Trial Outcomes & Findings for CCFZ533X2201 - PoC Study in de Novo Renal Transplantation (NCT NCT02217410)

Last Updated: 2021-09-28

Results Overview

Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Day 1

Results posted on

2021-09-28

Participant Flow

In Part 1, patients were enrolled into Arm 1. In Part 2, patients were randomized (2:1) to Arms 2A and 2B.

Study Part 1 focused on measuring the multiple-dose safety, tolerability, PK, and PD of both IV and SC CFZ533 when administered with the SoC treatment regimen. Study Part 2 investigated efficacy, safety, tolerability, PK and PD of CFZ533 in the absence of Tac.

Participant milestones

Participant milestones
Measure	CFZ533 + TAC + MMF (Part 1) CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	CFZ533 + MMF (Part 2) CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Overall Study STARTED	7	34	18
Overall Study COMPLETED	6	30	13
Overall Study NOT COMPLETED	1	4	5

Reasons for withdrawal

Reasons for withdrawal
Measure	CFZ533 + TAC + MMF (Part 1) CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	CFZ533 + MMF (Part 2) CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Overall Study Graft Loss	0	0	2
Overall Study Withdrawal by Subject	0	0	2
Overall Study Lost to Follow-up	0	0	1
Overall Study Lack of Efficacy	0	1	0
Overall Study Physician Decision	1	3	0

Baseline Characteristics

CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	CFZ533 + MMF (Part 2) n=34 Participants CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Tac + MMF (Part 2) n=18 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]	Total n=59 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 9.30 • n=5 Participants	49.0 years STANDARD_DEVIATION 15.79 • n=7 Participants	53.4 years STANDARD_DEVIATION 18.01 • n=5 Participants	50.1 years STANDARD_DEVIATION 15.91 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	26 Participants n=7 Participants	12 Participants n=5 Participants	42 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	20 Participants n=7 Participants	9 Participants n=5 Participants	31 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	27 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1

Population: The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data.

Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Mean Cmax Pharmacokinetic Parameter- Part I	66.3 ug/mL Standard Deviation 12.3	—

PRIMARY outcome

Timeframe: Day 1

Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Mean Tmax Pharmacokinetic Parameter - Part I	0.237 day Interval 0.0 to 1.02	—

PRIMARY outcome

Timeframe: Day 1

Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Mean AUClast Pharmacokinetic Parameter - Part I	367 day*ug/mL Standard Deviation 52.0	—

PRIMARY outcome

Timeframe: 3, 6, 9, and 12 months

Population: PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data.

To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=33 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=18 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II Month 3	6 events	2 events
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II Month 6	7 events	3 events
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II Month 9	7 events	3 events
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II Month 12	7 events	3 events

SECONDARY outcome

Timeframe: Baseline to end of study (Day 1, Day 29, Day 337)

Population: PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data.

To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=7 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Baseline	4.03 ng/ml Standard Deviation 4.08	0.125 ng/ml Standard Deviation 0.007
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 1	8.86 ng/ml Standard Deviation 0.0585	0.0585 ng/ml Standard Deviation 0.0711
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 2	16.7 ng/ml Standard Deviation 4.51	0.139 ng/ml Standard Deviation 0.193
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 3	24.8 ng/ml Standard Deviation 4.47	0.157 ng/ml Standard Deviation 0.235
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 4	31.3 ng/ml Standard Deviation 6.34	0.241 ng/ml Standard Deviation 0.418
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 8	54.0 ng/ml Standard Deviation 11.2	0.399 ng/ml Standard Deviation 0.636
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 15	84.1 ng/ml Standard Deviation 13.8	0.0879 ng/ml Standard Deviation 0.139
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 22	102 ng/ml Standard Deviation 13.9	0.0500 ng/ml Standard Deviation 0.132
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 29	120 ng/ml Standard Deviation 15.7	0.225 ng/ml Standard Deviation 0.504
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 36	128 ng/ml Standard Deviation 19.2	0.116 ng/ml Standard Deviation 0.2
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 43	145 ng/ml Standard Deviation 25.6	0.0193 ng/ml Standard Deviation 0.0474
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 50	156 ng/ml Standard Deviation 6.35	0.0478 ng/ml Standard Deviation 0.0687
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 57	161 ng/ml Standard Deviation 21.2	0 ng/ml Standard Deviation 0
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 64	163 ng/ml Standard Deviation 24.2	0.0316 ng/ml Standard Deviation 0.0492
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 71	156 ng/ml Standard Deviation 19.2	0.0148 ng/ml Standard Deviation 0.0363
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 85	168 ng/ml Standard Deviation 21.4	0.0139 ng/ml Standard Deviation 0.0340
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 99	155 ng/ml Standard Deviation 23.3	0 ng/ml Standard Deviation 0
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 113	85.7 ng/ml Standard Deviation 47.9	0.0668 ng/ml Standard Deviation 0.164
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 Day 127	12.2 ng/ml Standard Deviation 15.7	0.0488 ng/ml Standard Deviation 0.0697
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 EoS	0.918 ng/ml Standard Deviation 0.330	0.0184 ng/ml Standard Deviation 0.0411

SECONDARY outcome

Timeframe: Baseline to end of study (Day 1/predose)

Population: PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data.

The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=26 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=29 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (Baseline)	31508.33 MESF Standard Deviation 12759.49	14581.43 MESF Standard Deviation 9342.79
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (Baseline)	30836.00 MESF Standard Deviation 13648.69	12778.80 MESF Standard Deviation 7873.76
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D1 - 6h post dose)	1623.81 MESF Standard Deviation 1359.85	13806.90 MESF Standard Deviation 7185.66
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D15)	799.62 MESF Standard Deviation 762.38	15160.38 MESF Standard Deviation 7398.57
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D 29)	817.63 MESF Standard Deviation 1540.16	13299.60 MESF Standard Deviation 6330.89
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D 57)	597.13 MESF Standard Deviation 523.55	12234.38 MESF Standard Deviation 6943.13
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D 85)	635.47 MESF Standard Deviation 614.68	9330.86 MESF Standard Deviation 8484.46
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (D 197)	3699.0 MESF Standard Deviation 7298.98	2820.72 MESF Standard Deviation 2347.11
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (253)	2667.38 MESF Standard Deviation 6146.86	1427.14 MESF Standard Deviation 740.48
Free CD40 and Total CD40 on B Cells - Part II CFZ553 + MMF (EoS)	176.17 MESF Standard Deviation 266.82	1069.67 MESF Standard Deviation 809.12
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D1 - 6h post dose)	26437.65 MESF Standard Deviation 11930.50	13715.00 MESF Standard Deviation 8293.33
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D15)	24441.67 MESF Standard Deviation 9125.93	13707.14 MESF Standard Deviation 6770.14
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D29)	27840.00 MESF Standard Deviation 12106.72	12698.75 MESF Standard Deviation 6002.96
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D57)	27994.29 MESF Standard Deviation 12004.57	12583.85 MESF Standard Deviation 6210.07
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D85)	25044.00 MESF Standard Deviation 10896.65	8701.54 MESF Standard Deviation 4183.00
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D197)	21360.00 MESF Standard Deviation 3155.67	2067.60 MESF Standard Deviation 1617.28
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (D253)	15752.75 MESF Standard Deviation 7145.32	1750.50 MESF Standard Deviation 1005.84
Free CD40 and Total CD40 on B Cells - Part II Tac + MMF (EoS)	21200.00 MESF Standard Deviation 4407.95	6276.17 MESF Standard Deviation 11271.20

SECONDARY outcome

Timeframe: Baseline to end of study

Population: Safety analysis set included all patients that received at least one dose of study drug.

To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=7 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Anti-CFZ533 Antibodies - Part I	0 anti-CFZ533 antibodies	—

SECONDARY outcome

Timeframe: Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)

Population: Safety analysis set included all patients that received at least one dose of study drug. For Part 2, all patients that received their transplant along with any patient who received study drug but had no transplant were combined.

To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=34 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=18 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Anti-CFZ533 Antibodies - Part II Screening	0 anti-CFZ533 antibodies	0 anti-CFZ533 antibodies
Anti-CFZ533 Antibodies - Part II Baseline	0 anti-CFZ533 antibodies	—
Anti-CFZ533 Antibodies - Part II Day 141	0 anti-CFZ533 antibodies	0 anti-CFZ533 antibodies
Anti-CFZ533 Antibodies - Part II Day 225	0 anti-CFZ533 antibodies	0 anti-CFZ533 antibodies
Anti-CFZ533 Antibodies - Part II Day 309	0 anti-CFZ533 antibodies	0 anti-CFZ533 antibodies
Anti-CFZ533 Antibodies - Part II Study Completion	0 anti-CFZ533 antibodies	0 anti-CFZ533 antibodies

SECONDARY outcome

Timeframe: Day 1, Day 29, Day 337,

Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=32 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=18 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
eGFR - Part II Day 1	9.8 ml/min Interval 8.3 to 11.3	9.7 ml/min Interval 7.7 to 11.8
eGFR - Part II Day 29	55.6 ml/min Interval 50.4 to 60.7	44.3 ml/min Interval 37.2 to 51.4
eGFR - Part II Day 337	58.2 ml/min Interval 52.2 to 64.2	44.2 ml/min Interval 36.1 to 52.3

SECONDARY outcome

Timeframe: throughout study period (day 84 to day 336)

Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen.

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=32 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
CFZ533 Plasma PK Concentrations - Part II Day 84	247 ug/mL Standard Deviation 58.2	—
CFZ533 Plasma PK Concentrations - Part II Day 112	211 ug/mL Standard Deviation 51.8	—
CFZ533 Plasma PK Concentrations - Part II Day 140	178 ug/mL Standard Deviation 54.9	—
CFZ533 Plasma PK Concentrations - Part II Day 168	157 ug/mL Standard Deviation 57.4	—
CFZ533 Plasma PK Concentrations - Part II Day 196	148 ug/mL Standard Deviation 53.1	—
CFZ533 Plasma PK Concentrations - Part II Day 224	147 ug/mL Standard Deviation 53.8	—
CFZ533 Plasma PK Concentrations - Part II Day 252	151 ug/mL Standard Deviation 35.2	—
CFZ533 Plasma PK Concentrations - Part II Day 280	160 ug/mL Standard Deviation 87.7	—
CFZ533 Plasma PK Concentrations - Part II Day 308	132 ug/mL Standard Deviation 42.5	—
CFZ533 Plasma PK Concentrations - Part II Day 336	156 ug/mL Standard Deviation 85.2	—
CFZ533 Plasma PK Concentrations - Part II End of study	133 ug/mL Standard Deviation 57.8	—

SECONDARY outcome

Timeframe: 12 months

Population: PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data.

To quantify the change from baseline and recovery of peripheral blood total soluble CD40

Outcome measures

Outcome measures
Measure	CFZ533 + TAC + MMF (Part 1) n=32 Participants CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	Tac + MMF (Part 2) n=17 Participants Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Total sCD40 Plasma Concentrations - Part II Baseline	3.02 ng/mL Standard Deviation 2.44	3.67 ng/mL Standard Deviation 2.15
Total sCD40 Plasma Concentrations - Part II Day 1	6.95 ng/mL Standard Deviation 4.29	1.16 ng/mL Standard Deviation 1.15
Total sCD40 Plasma Concentrations - Part II Day 4	24.6 ng/mL Standard Deviation 11.0	1.16 ng/mL Standard Deviation 1.15
Total sCD40 Plasma Concentrations - Part II Day 15	69.6 ng/mL Standard Deviation 21.5	0.869 ng/mL Standard Deviation 1.55
Total sCD40 Plasma Concentrations - Part II Day 29	101 ng/mL Standard Deviation 18.9	0.362 ng/mL Standard Deviation 0.0746
Total sCD40 Plasma Concentrations - Part II Day 57	140 ng/mL Standard Deviation 17.4	0.438 ng/mL Standard Deviation 0.316
Total sCD40 Plasma Concentrations - Part II Day 85	189 ng/mL Standard Deviation 76.4	0.429 ng/mL Standard Deviation 0.324
Total sCD40 Plasma Concentrations - Part II Day 113	215 ng/mL Standard Deviation 75.5	0.391 ng/mL Standard Deviation 0.129
Total sCD40 Plasma Concentrations - Part II Day 141	237 ng/mL Standard Deviation 93.1	0.453 ng/mL Standard Deviation 0.271
Total sCD40 Plasma Concentrations - Part II Day 169	238 ng/mL Standard Deviation 80.3	0.537 ng/mL Standard Deviation 0.215
Total sCD40 Plasma Concentrations - Part II Day 197	253 ng/mL Standard Deviation 81.3	0.423 ng/mL Standard Deviation 0.0908
Total sCD40 Plasma Concentrations - Part II Day 225	258 ng/mL Standard Deviation 77.7	0.452 ng/mL Standard Deviation 0.119
Total sCD40 Plasma Concentrations - Part II Day 253	236 ng/mL Standard Deviation 36.5	0.457 ng/mL Standard Deviation 0.0800
Total sCD40 Plasma Concentrations - Part II Day 281	273 ng/mL Standard Deviation 71.3	0.455 ng/mL Standard Deviation 0.0789
Total sCD40 Plasma Concentrations - Part II Day 309	286 ng/mL Standard Deviation 66.0	0.454 ng/mL Standard Deviation 0.0957
Total sCD40 Plasma Concentrations - Part II Day 337	298 ng/mL Standard Deviation 57.4	0.411 ng/mL Standard Deviation 0.0581
Total sCD40 Plasma Concentrations - Part II End of Study	303 ng/mL Standard Deviation 59.7	0.959 ng/mL Standard Deviation 1.88

Adverse Events

CFZ533 + TAC + MMF (Part 1)

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

CFZ533 + MMF (Part 2)

Serious events: 21 serious events

Other events: 33 other events

Deaths: 0 deaths

Tac + MMF (Part 2)

Serious events: 12 serious events

Other events: 18 other events

Deaths: 0 deaths

Total

Serious events: 37 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Serious adverse events
Measure	CFZ533 + TAC + MMF (Part 1) n=7 participants at risk CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	CFZ533 + MMF (Part 2) n=34 participants at risk CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Tac + MMF (Part 2) n=18 participants at risk Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]	Total n=59 participants at risk Total
Blood and lymphatic system disorders Leukopenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Atrial fibrillation	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Photophobia	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Vision blurred	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Inguinal hernia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Mouth ulceration	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Nausea	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Pancreatitis	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Vomiting	28.6% 2/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Immune system disorders Kidney transplant rejection	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	14.7% 5/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	10.2% 6/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Immune system disorders Transplant rejection	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Bacteraemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Cytomegalovirus infection	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.8% 3/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.5% 5/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Encephalitis	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Enterobacter bacteraemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Gastroenteritis	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Gastrointestinal infection	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Hepatitis C	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Polyomavirus-associated nephropathy	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.8% 4/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.5% 5/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Pyelonephritis	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	16.7% 3/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.5% 5/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Renal cyst infection	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Infections and infestations Urosepsis	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Arteriovenous fistula aneurysm	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Complications of transplanted kidney	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	6.8% 4/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Delayed graft function	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Graft loss	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Incarcerated incisional hernia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Transplant dysfunction	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Injury, poisoning and procedural complications Transplant failure	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Investigations Amylase increased	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Investigations Blood creatinine increased	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.

Other adverse events
Measure	CFZ533 + TAC + MMF (Part 1) n=7 participants at risk CFZ533 (3 mg/kg SC) administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).	CFZ533 + MMF (Part 2) n=34 participants at risk CFZ533 (10mg/kg IV) administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction	Tac + MMF (Part 2) n=18 participants at risk Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]	Total n=59 participants at risk Total
Blood and lymphatic system disorders Anaemia	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.8% 3/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	22.2% 4/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	13.6% 8/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Leukocytosis	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.8% 3/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	10.2% 6/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Leukopenia	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	38.2% 13/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	16.7% 3/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	28.8% 17/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Nephrogenic anaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Neutropenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.1% 2/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Normocytic anaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Polycythaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Angina pectoris	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Arrhythmia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Atrial fibrillation	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.9% 2/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Bradycardia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Extrasystoles	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Myocardial infarction	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Palpitations	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Sinus tachycardia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Tachycardia	28.6% 2/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.8% 4/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.9% 7/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Congenital, familial and genetic disorders Hydrocele	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Ear and labyrinth disorders Ear discomfort	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Ear and labyrinth disorders Vertigo	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Endocrine disorders Hyperparathyroidism	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Endocrine disorders Hyperparathyroidism secondary	28.6% 2/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.1% 3/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Chalazion	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Dry eye	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Eye movement disorder	28.6% 2/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Ocular hyperaemia	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Eye disorders Retinal vein occlusion	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal distension	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.8% 3/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	16.7% 3/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	11.9% 7/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	14.7% 5/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	8.5% 5/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Anal fissure	0.00% 0/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	5.6% 1/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	1.7% 1/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.
Gastrointestinal disorders Aphthous ulcer	14.3% 1/7 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	2.9% 1/34 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	0.00% 0/18 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.	3.4% 2/59 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.