Trial Outcomes & Findings for An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma (NCT NCT00552396)

NCT ID: NCT00552396

Last Updated: 2016-03-31

Results Overview

The maximum tolerated dose (MTD) is the highest dose level below the maximum administered dose (MAD) where none or 1 out of 6 subjects have a DLT.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: From start of the treatment to end of study
• Results posted on: 2016-03-31

Participant Flow

32 subjects were enrolled and 21 subjects were screen failures

Participant milestones

Measure	0.0003 mg/kg 3+3 design was employed for the first dosing cycle at each dose level. The 7 dose levels were 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. The subjects received up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks.	0.003 mg/kg	0.015 mg/kg	0.075 mg/kg	0.3 mg/kg	1 mg/kg	3 mg/kg
Overall Study STARTED	4	3	3	6	3	3	10
Overall Study COMPLETED	1	0	0	0	0	0	1
Overall Study NOT COMPLETED	3	3	3	6	3	3	9

Reasons for withdrawal

Measure	0.0003 mg/kg 3+3 design was employed for the first dosing cycle at each dose level. The 7 dose levels were 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. The subjects received up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks.	0.003 mg/kg	0.015 mg/kg	0.075 mg/kg	0.3 mg/kg	1 mg/kg	3 mg/kg
Overall Study protocol withdrawal criteria	3	3	3	6	3	3	9

Baseline Characteristics

An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma

Baseline characteristics by cohort

Measure	0.0003 mg/kg n=4 Participants	0.003 mg/kg n=3 Participants	0.015 mg/kg n=3 Participants	0.075 mg/kg n=6 Participants	0.3 mg/kg n=3 Participants	1 mg/kg n=3 Participants	3 mg/kg n=10 Participants	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	7 Participants n=115 Participants	21 Participants n=24 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants	11 Participants n=24 Participants
Age, Continuous	62.3 years STANDARD_DEVIATION 4.03 • n=5 Participants	49.7 years STANDARD_DEVIATION 2.52 • n=7 Participants	66 years STANDARD_DEVIATION 11.53 • n=5 Participants	64 years STANDARD_DEVIATION 5.51 • n=4 Participants	62.7 years STANDARD_DEVIATION 11.02 • n=21 Participants	60.3 years STANDARD_DEVIATION 7.57 • n=10 Participants	60.6 years STANDARD_DEVIATION 18.68 • n=115 Participants	61.1 years STANDARD_DEVIATION 10.78 • n=24 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	4 Participants n=115 Participants	13 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants	19 Participants n=24 Participants
Region of Enrollment United States	4 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	6 participants n=4 Participants	3 participants n=21 Participants	3 participants n=10 Participants	10 participants n=115 Participants	32 participants n=24 Participants

PRIMARY outcome

Timeframe: From start of the treatment to end of study

Population: All treated participants who received at least one dose of the study drug and were evaluable for DLT

The maximum tolerated dose (MTD) is the highest dose level below the maximum administered dose (MAD) where none or 1 out of 6 subjects have a DLT.

Outcome measures

Measure	IPH2101 0.0003 mg/kg n=4 Participants Participants were administered an IV dose of 0.0003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.003 mg/kg n=3 Participants Participants were administered an IV dose of 0.003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.015 mg/kg n=3 Participants Participants were administered an IV dose of 0.015 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.075 mg/kg n=6 Participants Participants were administered an IV dose of 0.075 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.3mg/kg n=3 Participants Participants were administered an IV dose of 0.3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 1mg/kg n=3 Participants Participants were administered an IV dose of 1 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 3 mg/kg n=10 Participants Participants were administered an IV dose of 3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level.If MTD this is not reached at 3mg/kg, 7 subjects will be enrolled at this dose to obtain more data from a larger subject pool to better evaluate safety, PK, PD and signs of efficacy.
Maximum Tolerated Dose (MTD) of IPH2101 as Determined by Number of Participants With Dose-Limiting Toxicities (DLTs) Related to IPH2101 Treatment	0 Number of participants with DLT	0 Number of participants with DLT	0 Number of participants with DLT	1 Number of participants with DLT	0 Number of participants with DLT	0 Number of participants with DLT	0 Number of participants with DLT

SECONDARY outcome

Timeframe: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration

Cmax was obtained from the plasma concentration versus time data after IV administration of IPH2101.

Outcome measures

Measure	IPH2101 0.0003 mg/kg n=2 Participants Participants were administered an IV dose of 0.0003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.003 mg/kg n=3 Participants Participants were administered an IV dose of 0.003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.015 mg/kg n=3 Participants Participants were administered an IV dose of 0.015 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.075 mg/kg n=6 Participants Participants were administered an IV dose of 0.075 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.3mg/kg n=3 Participants Participants were administered an IV dose of 0.3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 1mg/kg n=3 Participants Participants were administered an IV dose of 1 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 3 mg/kg n=10 Participants Participants were administered an IV dose of 3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level.If MTD this is not reached at 3mg/kg, 7 subjects will be enrolled at this dose to obtain more data from a larger subject pool to better evaluate safety, PK, PD and signs of efficacy.
Maximum Plasma Concentration (Cmax) of IPH2101 After Cycle 1 Administration	0 ng/mL Geometric Coefficient of Variation 0	45.8 ng/mL Geometric Coefficient of Variation 41.3	316 ng/mL Geometric Coefficient of Variation 53.8	1620 ng/mL Geometric Coefficient of Variation 38.4	4510 ng/mL Geometric Coefficient of Variation 30.9	24800 ng/mL Geometric Coefficient of Variation 25.5	55200 ng/mL Geometric Coefficient of Variation 31.7

SECONDARY outcome

Timeframe: Anti-KIR (1-7F9) concentrations were measured prior to infusion at 0.167, 1, 3, 6, 12 and 24 hours and then on Days 7, 14 and 21 after the start of the first dose administration

AUC(INF), area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration within the dosing interval was calculated for Cycle 1.

Outcome measures

Measure	IPH2101 0.0003 mg/kg n=2 Participants Participants were administered an IV dose of 0.0003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.003 mg/kg n=3 Participants Participants were administered an IV dose of 0.003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.015 mg/kg n=3 Participants Participants were administered an IV dose of 0.015 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.075 mg/kg n=5 Participants Participants were administered an IV dose of 0.075 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.3mg/kg n=2 Participants Participants were administered an IV dose of 0.3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 1mg/kg n=3 Participants Participants were administered an IV dose of 1 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 3 mg/kg n=10 Participants Participants were administered an IV dose of 3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level.If MTD this is not reached at 3mg/kg, 7 subjects will be enrolled at this dose to obtain more data from a larger subject pool to better evaluate safety, PK, PD and signs of efficacy.
Area Under the Plasma-concentration-time Curve [AUC (INF)] of IPH2101 After Cycle 1 Administration	0 ng*hours/ml Geometric Coefficient of Variation 0	808 ng*hours/ml Geometric Coefficient of Variation 49.7	16593 ng*hours/ml Geometric Coefficient of Variation 273.3	161811 ng*hours/ml Geometric Coefficient of Variation 61.5	596308 ng*hours/ml Geometric Coefficient of Variation 0	4331537 ng*hours/ml Geometric Coefficient of Variation 60.7	9292602 ng*hours/ml Geometric Coefficient of Variation 41.7

SECONDARY outcome

Timeframe: From start of the treatment to end of study or disease progression

Disease Response Assessment by Principal Investigator and Sponsor(Efficacy Population).Stable Disease was defined as not meeting criteria for complete response, very good partial response, partial response, or progressive disease

Outcome measures

Measure	IPH2101 0.0003 mg/kg n=1 Participants Participants were administered an IV dose of 0.0003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.003 mg/kg n=2 Participants Participants were administered an IV dose of 0.003 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.015 mg/kg n=2 Participants Participants were administered an IV dose of 0.015 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.075 mg/kg n=5 Participants Participants were administered an IV dose of 0.075 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 0.3mg/kg Participants were administered an IV dose of 0.3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 1mg/kg n=3 Participants Participants were administered an IV dose of 1 mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level. If no dose limiting toxicity (DLT) was observed, the dose was escalated to next higher level. If a DLT was observed among 1 of 3 treated participants in the first course at a dose level, 3 participants were additionally enrolled and treated at the same dose level. If no further DLT was observed during the first course in these additional participants, the dose was escalated to next higher dose level.	IPH2101 3 mg/kg n=6 Participants Participants were administered an IV dose of 3mg/kg IPH2101 every 4 weeks for 4 cycles. Initially, 3 participants were treated at one dose level.If MTD this is not reached at 3mg/kg, 7 subjects will be enrolled at this dose to obtain more data from a larger subject pool to better evaluate safety, PK, PD and signs of efficacy.
Number of Evaluable Patients With Stable Disease. "Evaluable" is Defined as 2 Consecutive M Protein Assessments	1 Number of participants	1 Number of participants	1 Number of participants	3 Number of participants	—	2 Number of participants	3 Number of participants

Adverse Events

0.0003 mg/kg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

0.003 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

0.015 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

0.075 mg/kg

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

0.3 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

1 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

3 mg/kg

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	0.0003 mg/kg n=4 participants at risk 3+3 design was employed for the first dosing cycle at each dose level. The 7 dose levels were 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. The subjects received up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks.	0.003 mg/kg n=3 participants at risk	0.015 mg/kg n=3 participants at risk	0.075 mg/kg n=6 participants at risk	0.3 mg/kg n=3 participants at risk	1 mg/kg n=3 participants at risk	3 mg/kg n=10 participants at risk
Nervous system disorders Headeache	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
General disorders Non cardiac chest pain	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Infection	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations Decreased platelets	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Renal and urinary disorders Acute Renal failure	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations Increased creatinine	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) progression of disease	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Musculoskeletal and connective tissue disorders worsening back pain	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders worsening nausea	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Pneumonia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Streptococcal pneumonia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations infection with grade 4 neutrophil	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations elevated creatinine	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).

Other adverse events

Measure	0.0003 mg/kg n=4 participants at risk 3+3 design was employed for the first dosing cycle at each dose level. The 7 dose levels were 0.0003 mg/kg, 0.003 mg/kg, 0.015 mg/kg, 0.075 mg/kg, 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg. The subjects received up to a total of 4 administrations of Anti-KIR (1-7F9) with a dosing interval between each administration of 4 weeks.	0.003 mg/kg n=3 participants at risk	0.015 mg/kg n=3 participants at risk	0.075 mg/kg n=6 participants at risk	0.3 mg/kg n=3 participants at risk	1 mg/kg n=3 participants at risk	3 mg/kg n=10 participants at risk
General disorders fatigue	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	50.0% 3/6 • Number of events 3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	66.7% 2/3 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	40.0% 4/10 • Number of events 4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
General disorders chills	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
General disorders Non Cardiac chest pain	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
General disorders pyrexia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	30.0% 3/10 • Number of events 3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
General disorders edema peripheral	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders Diarrhea	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	30.0% 3/10 • Number of events 3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders Nausea	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders Constipation	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders vomiting	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations upper respiratory tract infection	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Pneumonia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Sinusitis	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Infections and infestations Urinary tract infection	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations hemoglobin decreased	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations neutrophil count decreased	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations blood creatinin increased	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations lymphocyte count decreased	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations platelet count decreased	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Investigations white blood cell count decreased	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders hyponatremia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	66.7% 4/6 • Number of events 4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders anorexia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders dehydration	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders hyperglycemia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Metabolism and nutrition disorders hypocalcemia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	20.0% 2/10 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Respiratory, thoracic and mediastinal disorders dyspnea	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	50.0% 3/6 • Number of events 3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Respiratory, thoracic and mediastinal disorders oropharyngeal pain	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Musculoskeletal and connective tissue disorders back pain	25.0% 1/4 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Musculoskeletal and connective tissue disorders musculoskeletal pain	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 2/6 • Number of events 2 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Nervous system disorders headache	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	50.0% 3/6 • Number of events 3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Skin and subcutaneous tissue disorders rash	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Blood and lymphatic system disorders anemia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/6 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Cardiac disorders tachycardia	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	33.3% 1/3 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/10 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).
Surgical and medical procedures sinus operation	0.00% 0/4 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	16.7% 1/6 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	0.00% 0/3 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).	10.0% 1/10 • Number of events 1 • Adverse events were collected from screening and until the end of study at each study visit. Maximal study duration according to dose level was 4 to 9 months. All participants who received at least one dose of the study drug (safety population).

Additional Information

Dr Renaud Buffet Senior Director, Clinical Development and Translational Research

Innate Pharma

Phone: +33430303032

Email: renaud.buffet@innate-pharma.fr

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60