Trial Outcomes & Findings for Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients (NCT NCT02268526)

NCT ID: NCT02268526

Last Updated: 2021-01-05

Results Overview

Number of participants who require preemptive HCMV therapy. The definition of requiring preemptive anti-HCMV therapy was meeting either one of the following conditions: 1. the plasma HCMV DNA level is \>= 1000 copies/mL (with or without HCMV disease) or 2. the plasma HCMV DNA level is \< 1000 copies/mL, but HCMV disease was reported

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 86 participants
• Primary outcome timeframe: 98 days
• Results posted on: 2021-01-05

Participant Flow

Cohort 1: Six patients were planned for enrollment; 6 patients were enrolled. Cohort 2: Eighty patients were planned and 80 were enrolled.

Participant milestones

Measure	Cohort 1: CSJ148 Cohort 1: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Overall Study STARTED	6	59	21
Overall Study PD Analysis Set (Cohort 2)	0	42	17
Overall Study COMPLETED	5	38	16
Overall Study NOT COMPLETED	1	21	5

Reasons for withdrawal

Measure	Cohort 1: CSJ148 Cohort 1: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Overall Study Adverse Event	0	2	1
Overall Study Death	1	11	0
Overall Study protocol deviation	0	1	0
Overall Study Physician Decision	0	0	1
Overall Study Subject/guardian decision	0	7	3

Baseline Characteristics

Efficacy and Safety Study of CSJ148 in Stem Cell Transplant Patients

Baseline characteristics by cohort

Measure	Cohort 1: CSJ148 n=6 Participants Cohort 1: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=59 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo n=21 Participants Cohort 2: Placebo IV q 4weeks	Total n=86 Participants Total of all reporting groups
Age, Continuous	52.8 years STANDARD_DEVIATION 8.70 • n=5 Participants	54.7 years STANDARD_DEVIATION 12.33 • n=7 Participants	46.0 years STANDARD_DEVIATION 14.33 • n=5 Participants	52.5 years STANDARD_DEVIATION 13.04 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	23 Participants n=7 Participants	6 Participants n=5 Participants	31 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	36 Participants n=7 Participants	15 Participants n=5 Participants	55 Participants n=4 Participants

PRIMARY outcome

Timeframe: 98 days

Population: Full Analysis Set - included all 86 patients enrolled in the study

Number of participants who require preemptive HCMV therapy. The definition of requiring preemptive anti-HCMV therapy was meeting either one of the following conditions: 1. the plasma HCMV DNA level is >= 1000 copies/mL (with or without HCMV disease) or 2. the plasma HCMV DNA level is < 1000 copies/mL, but HCMV disease was reported

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=59 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo n=21 Participants Cohort 2: Placebo IV q 4weeks
Number of Participants Who Require Preemptive HCMV Therapy	24 Count of Participants	23 Count of Participants	9 Count of Participants

PRIMARY outcome

Timeframe: 98 days

Population: Safety Analysis Set- Eighty-six patients were enrolled in the study and all were included in the safety analysis set

Number of participants with adverse events as a measure of safety and tolerability. Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses.

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=21 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Number of Participants With Adverse Events as a Measure of Safety and Tolerability At least one treatment-emergent AE	65 Count of Participants	21 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability At least one drug-related AE	0 Count of Participants	2 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability At least one SAE	46 Count of Participants	15 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability At least one drug-related SAE	0 Count of Participants	1 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Deaths	12 Count of Participants	0 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability At least 1 treatment-emergent AE grade 3 or higher	58 Count of Participants	17 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Total deaths:those reported after study completion	19 Count of Participants	3 Count of Participants	—
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Discontinued study treatment due to any AE	1 Count of Participants	1 Count of Participants	—

SECONDARY outcome

Timeframe: 98 days

Population: PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded.

The time to start preemptive therapy is defined as the number of days between initial dose of study drug and the earlier of (1) the start of preemptive therapy, and (2) the development of HCMV disease or death due to HCMV disease, or (3) censored at the EoT visit if no therapy required for Cohort 2

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=42 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=17 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Time to Start of Preemptive HCMV Therapy Cohort 2	62.03 days Standard Deviation 12.145	49.54 days Standard Deviation 13.470	—

SECONDARY outcome

Timeframe: 98 days

Population: PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded.

Among those who required preemptive therapy, the number of times preemptive therapy was required. (Cohort 2)

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=42 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=17 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Number of Times That Preemptive HCMV Therapy is Required -Cohort 2	2.070 number of times Interval 1.369 to 3.13	2.540 number of times Interval 1.342 to 4.806	—

SECONDARY outcome

Timeframe: 98 days

Population: PD analysis set (Cohort 2) -included 59 patients, 27 patients (31%) were excluded.

Proportion of participants developing HCMV disease

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=42 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 n=17 Participants Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Proportion of Participants Developing HCMV Disease	0.119 proportion of participants Interval 0.048 to 0.234	0 proportion of participants Interval 0.0 to 0.162	—

SECONDARY outcome

Timeframe: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

PK parameters were calculated from plasma concentration-time data using non-compartmental methods. The AUCtau was calculated using a linear trapezoidal method

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only Day 1	7310 day*ug/mL Standard Deviation 2310	—	—
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only Day 29	9890 day*ug/mL Standard Deviation 3470	—	—
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only Day 57	11400 day*ug/mL Standard Deviation 4020	—	—
Area Under the Serum Concentration-time Curve During the Dosing Interval (AUCtau) for CSJ148 Only Day 85	12900 day*ug/mL Standard Deviation 4380	—	—

SECONDARY outcome

Timeframe: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

Cmax is the observed maximum plasma (or serum or blood) concentration following drug administration [ug / mL] for CSJ148 only

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only Day 85	1230 ug/mL Standard Deviation 458	—	—
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only Day 1	1040 ug/mL Standard Deviation 356	—	—
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only Day 29	1100 ug/mL Standard Deviation 282	—	—
Maximum Serum Concentration During the Dosing Interval (Cmax) for CSJ148 Only Day 57	1180 ug/mL Standard Deviation 316	—	—

SECONDARY outcome

Timeframe: Day 1, Day 29, Day 57, Day 85 at predose (0hr) and 3,6,24 hrs post dose

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

Ctrough is The observed plasma (or serum or blood) concentration at the end of a drug administration dosing interval [ug / mL]

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Trough Serum Concentration (Ctrough) for CSJ148 Only Day 1	104 ug/mL Standard Deviation 59.7	—	—
Trough Serum Concentration (Ctrough) for CSJ148 Only Day 29	167 ug/mL Standard Deviation 85.5	—	—
Trough Serum Concentration (Ctrough) for CSJ148 Only Day 57	214 ug/mL Standard Deviation 152	—	—
Trough Serum Concentration (Ctrough) for CSJ148 Only Day 85	223 ug/mL Standard Deviation 104	—	—

SECONDARY outcome

Timeframe: Day 1 and Day 85

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

Accumulation ratio(Racc) is Racc: Accumulation ratio, calculated by AUCtau (Day 85) divided by AUCtau (for the 1st dose at Day 1).

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Accumulation Ratio(Racc) for CSJ148 Only at Day 85	1.83 Ratio Standard Deviation 0.531	—	—

SECONDARY outcome

Timeframe: Day 85

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

Lambda_z is the terminal elimination rate constant [1/day] at Day 85

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Lambda_z for CSJ148 Only at Day 85	0.0409 1/day Standard Deviation 0.0175	—	—

SECONDARY outcome

Timeframe: Day 85

Population: Pharmacokinetics (PK) analysis set (CSJ148 only)- The PK analysis set included the 65 patients who received a dose of CSJ148

T1/2 is the terminal elimination half-life [time]

Outcome measures

Measure	Total CSJ148 (Cohort 1 & Cohort 2) n=65 Participants Cohort 1: CSJ148 IV q 4weeks and Cohort 2: CSJ148 IV q 4weeks	Cohort 2: CSJ148 Cohort 2: CSJ148 IV q 4weeks	Cohort 2: Placebo Cohort 2: Placebo IV q 4weeks
Half-life (T1/2) for CSJ148 Only at Day 85	19.7 day Standard Deviation 7.18	—	—

Adverse Events

Placebo

Serious events: 15 serious events

Other events: 21 other events

Deaths: 0 deaths

Total CSJ148

Serious events: 46 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=21 participants at risk Cohort 2: Placebo IV q 4weeks	Total CSJ148 n=65 participants at risk Cohort 1: CSJ148 IV q 4weeks \& Cohort 2: CSJ148 IV q 4weeks
Blood and lymphatic system disorders Anaemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Febrile neutropenia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Microangiopathic haemolytic anaemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Neutropenia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Splenic lesion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Thrombocytopenia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Thrombotic microangiopathy	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Atrial fibrillation	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Atrial flutter	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Bradycardia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Cardiac tamponade	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Intracardiac mass	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal pain	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Ascites	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Colitis erosive	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Haematemesis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Haemorrhoids	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Ileus	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Large intestinal ulcer	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Nausea	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Oedematous pancreatitis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Rectal lesion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Vomiting	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Non-cardiac chest pain	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Oedema peripheral	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Pyrexia	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Hepatic function abnormal	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Hepatic lesion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Hepatitis cholestatic	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Hyperbilirubinaemia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease in liver	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease in skin	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Anaphylactic shock	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Chronic graft versus host disease in liver	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Atypical pneumonia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Bacteraemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Bacteriuria	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Clostridium difficile colitis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Cytomegalovirus chorioretinitis	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Cytomegalovirus colitis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Cytomegalovirus gastritis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Cytomegalovirus infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Cytomegalovirus viraemia	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Disseminated tuberculosis	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Enterobacter bacteraemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Epididymitis tuberculous	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Epstein-Barr virus infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Escherichia bacteraemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Escherichia sepsis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Herpes zoster	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Human herpesvirus 6 infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations JC virus infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Klebsiella infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Meningoencephalitis herpetic	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Ophthalmic herpes zoster	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pneumonia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pneumonia bacterial	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pneumonia fungal	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pseudomonal bacteraemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pseudomonal sepsis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pseudomonas infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pulmonary tuberculosis	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Respiratory syncytial virus infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Rhinovirus infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Sepsis	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Septic shock	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Sinusitis	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Staphylococcal sepsis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Stenotrophomonas infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Upper respiratory tract infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Urinary tract infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Engraft failure	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Fall	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Hip fracture	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Transplant failure	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Alanine aminotransferase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Aspartate aminotransferase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Blood bilirubin increased	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Blood lactate dehydrogenase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Cytomegalovirus test positive	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Gamma-glutamyltransferase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Lipase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Dehydration	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hypophagia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Malnutrition	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia recurrent	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia recurrent	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Post transplant lymphoproliferative disorder	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer recurrent	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma recurrent	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Facial paresis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Metabolic encephalopathy	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Posterior reversible encephalopathy syndrome	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Somnolence	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Hallucination	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Mental status changes	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Acute kidney injury	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Renal disorder	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Asthma	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Dermatitis bullous	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Rash	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Vascular disorders Hypertension	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.

Other adverse events

Measure	Placebo n=21 participants at risk Cohort 2: Placebo IV q 4weeks	Total CSJ148 n=65 participants at risk Cohort 1: CSJ148 IV q 4weeks \& Cohort 2: CSJ148 IV q 4weeks
Blood and lymphatic system disorders Anaemia	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Febrile neutropenia	47.6% 10/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	38.5% 25/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Neutropenia	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Blood and lymphatic system disorders Thrombocytopenia	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Cardiac disorders Tachycardia	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Eye disorders Dry eye	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	21.5% 14/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal discomfort	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal distension	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal pain	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	24.6% 16/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Abdominal pain upper	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Constipation	38.1% 8/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	29.2% 19/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Diarrhoea	57.1% 12/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	66.2% 43/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Dry mouth	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	16.9% 11/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Dyspepsia	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Epigastric discomfort	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	3.1% 2/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Haemorrhoids	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	20.0% 13/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Lip dry	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Melaena	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Mouth haemorrhage	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Nausea	66.7% 14/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	69.2% 45/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Oesophagitis	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Stomatitis	71.4% 15/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	55.4% 36/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Tongue ulceration	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Gastrointestinal disorders Vomiting	66.7% 14/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	58.5% 38/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Asthenia	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Catheter site erythema	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Catheter site pain	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Chest discomfort	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Chills	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	23.1% 15/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Fatigue	33.3% 7/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	27.7% 18/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Generalised oedema	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Non-cardiac chest pain	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Oedema peripheral	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	18.5% 12/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Pain	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
General disorders Pyrexia	47.6% 10/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	58.5% 38/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Hepatobiliary disorders Hyperbilirubinaemia	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	15.4% 10/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease in intestine	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Acute graft versus host disease in skin	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	21.5% 14/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Chronic graft versus host disease	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Immune system disorders Chronic graft versus host disease in skin	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Candida infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Clostridium difficile infection	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Device related infection	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Folliculitis	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Herpes zoster	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Human herpesvirus 6 infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Oral candidiasis	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Oral herpes	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Papilloma viral infection	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Pneumonia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Rhinovirus infection	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Staphylococcal bacteraemia	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Upper respiratory tract infection	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Infections and infestations Urinary tract infection	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Fall	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Injury, poisoning and procedural complications Transfusion reaction	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Alanine aminotransferase increased	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Aspartate aminotransferase increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Blood bilirubin increased	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Investigations Blood creatinine increased	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Decreased appetite	33.3% 7/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	41.5% 27/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Fluid overload	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hyperglycaemia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hyperkalaemia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hypocalcaemia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hypokalaemia	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	30.8% 20/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hypomagnesaemia	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Metabolism and nutrition disorders Hypophosphataemia	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	18.5% 12/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Back pain	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	26.2% 17/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Bone pain	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Myalgia	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Dizziness	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	24.6% 16/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Headache	28.6% 6/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	36.9% 24/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Neuropathy peripheral	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Syncope	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Nervous system disorders Tremor	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Anxiety	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Confusional state	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Hallucination	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Insomnia	28.6% 6/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	23.1% 15/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Psychiatric disorders Sleep disorder	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Acute kidney injury	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Chronic kidney disease	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Dysuria	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Haematuria	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	15.4% 10/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Renal and urinary disorders Pollakiuria	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Reproductive system and breast disorders Scrotal pain	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	0.00% 0/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Cough	42.9% 9/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	38.5% 25/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	20.0% 13/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Epistaxis	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	12.3% 8/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Hiccups	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	10.8% 7/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	18.5% 12/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Productive cough	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	4.6% 3/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Blister	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	7.7% 5/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Dry skin	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Eczema	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Erythema	14.3% 3/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Petechiae	4.8% 1/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	6.2% 4/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Pruritus	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	27.7% 18/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Rash	33.3% 7/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	36.9% 24/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Rash generalised	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Rash macular	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	1.5% 1/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Skin and subcutaneous tissue disorders Urticaria	9.5% 2/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	9.2% 6/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Vascular disorders Hypertension	23.8% 5/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	35.4% 23/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.
Vascular disorders Hypotension	19.0% 4/21 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.	13.8% 9/65 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit 183 days. Additional 2 deaths in placebo occurred during follow-up (Day 100 to 183) after early treatment and study discontinuation. One additional placebo death occurred after end of study (Day 183) and 7 additional CSJ148 deaths occurred post end of study (Day 183). Patients treated with CSJ148 in Cohorts 1 and 2 were pooled to simplify the safety analyses because the dosage of CSJ148 was the same for each cohort. Cohort 1 was just a PK cohort with only 6 patients.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 8627788300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER