Trial Outcomes & Findings for ß-SPECIFIC 4 Patients: Study of Pediatric EffiCacy and Safety wIth FIrst-line Use of Canakinumab (NCT NCT02296424)

Last Updated: 2019-07-09

Results Overview

The primary efficacy variable for Part II was the proportion of patients in clinical remission on canakinumab 4 mg/kg (+/- concomitant NSAID only) who were able to remain on a reduced dose or on prolonged dose interval for at least 24 consecutive weeks. As the primary objective was to show statistically significance in at least one of canakinumab treatment arms (reduced dose and prolonged dose interval arms) in Part II then the Type I error rate 5% was controlled and split to 2.5%. Clinical remission per protocol is defined as the maintenance of inactive disease for at least 6 months (24consecutive weeks) while on therapy. The primary analysis considered both inactive disease status and the patient dose step duration. In the event the inactive disease status was missing, yet the patient remained at the same dose level through the next visit with the same disease status, it was concluded that inactive disease was maintained during this time period and was carried forward.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

182 participants

Primary outcome timeframe

baseline to 24 weeks

Results posted on

2019-07-09

Participant Flow

182 enrolled but 16 qualified immediately for Part II \& were randomized while 166 continued in Part I \& were treated with canakinumab 4 mg/kg every 4 weeks until study end unless they discontinued, or until they qualified for Part II. Of these, 40 discontinued. Most frequent reason was lack of efficacy

75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)

Participant milestones

Participant milestones
Measure	Cohort 1 Participants from study CACZ885G2301E1, aged ≥ 2 to \< 20 years at the time of the patient's first dose of canakinumab, who at the time of evaluation for participation in CACZ885G2306 were being treated with canakinumab 4mg/kg and had inactive disease	PART 1: Cohort 2 Participants who at screening were aged ≥ 2 to \< 20 years, had active SJIA (as per protocol), and were canakinumab treatment-naïve	Dose Reduction canakinumab 4 mg/kg every 4 weeks until study end unless discontinuation occurred, or until they qualified \& entered Part II	Dose Interval Prolongation canakinumab 4 mg/kg every 4 weeks until study end unless discontinuation occurred, or until they qualified \& entered Part II
Part 1 STARTED	84	98	0	0
Part 1 COMPLETED	61	65	0	0
Part 1 NOT COMPLETED	23	33	0	0
Part 2 STARTED	0	0	38	37
Part 2 COMPLETED	0	0	35	37
Part 2 NOT COMPLETED	0	0	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Participants from study CACZ885G2301E1, aged ≥ 2 to \< 20 years at the time of the patient's first dose of canakinumab, who at the time of evaluation for participation in CACZ885G2306 were being treated with canakinumab 4mg/kg and had inactive disease	PART 1: Cohort 2 Participants who at screening were aged ≥ 2 to \< 20 years, had active SJIA (as per protocol), and were canakinumab treatment-naïve	Dose Reduction canakinumab 4 mg/kg every 4 weeks until study end unless discontinuation occurred, or until they qualified \& entered Part II
Part 1 New therapy for study indication	0	1	0
Part 1 Protocol Violation	0	1	0
Part 1 Withdrawal by Subject	0	2	0
Part 1 Study terminated by sponsor	0	1	0
Part 1 Adverse Event	2	11	0
Part 1 Lack of Efficacy	5	17	0
Part 1 16 directly started part II	16	0	0
Part 2 Lack of Efficacy	0	0	1
Part 2 Adverse Event	0	0	1
Part 2 Lost to Follow-up	0	0	1

Baseline Characteristics

Safety Set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=68 Participants Participants from study CACZ885G2301E1, aged ≥ 2 to \< 20 years at the time of the patient's first dose of canakinumab, who at the time of evaluation for participation in CACZ885G2306 were being treated with canakinumab 4mg/kg and had inactive disease	Cohort 2 n=98 Participants Dose interval prologation All participants received canakinumab 4mg/kg (300 mg max) every 4 weeks in Part I of this study All participants in Part II of this study came from Part 1, So only Part 1 is shown here in Baseline Characteristics	Total n=166 Participants Total of all reporting groups
Age, Continuous Age (years)	11.8 Years STANDARD_DEVIATION 4.53 • n=68 Participants • Safety Set	8.3 Years STANDARD_DEVIATION 4.20 • n=98 Participants • Safety Set	9.7 Years STANDARD_DEVIATION 4.66 • n=166 Participants • Safety Set
Age, Customized >=2 - <4 years	1 participants n=1 Participants • Safety Set	14 participants n=14 Participants • Safety Set	15 participants n=15 Participants • Safety Set
Age, Customized >=4 - <6 years	6 participants n=6 Participants • Safety Set	17 participants n=17 Participants • Safety Set	23 participants n=23 Participants • Safety Set
Age, Customized >=6 - <12 years	24 participants n=24 Participants • Safety Set	42 participants n=42 Participants • Safety Set	66 participants n=66 Participants • Safety Set
Age, Customized >=12 - <20 years	34 participants n=34 Participants • Safety Set	25 participants n=25 Participants • Safety Set	59 participants n=59 Participants • Safety Set
Age, Customized >=20 years	3 participants n=3 Participants • Safety Set	—	3 participants n=3 Participants • Safety Set
Sex: Female, Male Female	34 Participants n=68 Participants • Safety Set	42 Participants n=98 Participants • Safety Set	76 Participants n=166 Participants • Safety Set
Sex: Female, Male Male	34 Participants n=68 Participants • Safety Set	56 Participants n=98 Participants • Safety Set	90 Participants n=166 Participants • Safety Set
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=68 Participants	1 Participants n=98 Participants	1 Participants n=166 Participants
Race (NIH/OMB) Asian	0 Participants n=68 Participants	2 Participants n=98 Participants	2 Participants n=166 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=68 Participants	0 Participants n=98 Participants	0 Participants n=166 Participants
Race (NIH/OMB) Black or African American	1 Participants n=68 Participants	1 Participants n=98 Participants	2 Participants n=166 Participants
Race (NIH/OMB) White	66 Participants n=68 Participants	81 Participants n=98 Participants	147 Participants n=166 Participants
Race (NIH/OMB) More than one race	1 Participants n=68 Participants	12 Participants n=98 Participants	13 Participants n=166 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	1 Participants n=98 Participants	1 Participants n=166 Participants

PRIMARY outcome

Timeframe: baseline to 24 weeks

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Canakinumab Dose Reduction n=38 Participants Cohort 1 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)	Canakinumab Dose Interval Prolongation n=37 Participants Cohort 2 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)
Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval. Able to remain on dose	27 particiapants	31 particiapants
Number of Participants in Clinical Remission on Canakinumab Who Are Able to Remain at an Initial Reduced Canakinumab Dose or Prolonged Canakinumab Dose Interval. Not able to remain on dose	11 particiapants	6 particiapants

SECONDARY outcome

Timeframe: During study parts I and II. The estimated study duration is not more than 216 weeks (with an average expected duration of 108 weeks).

Population: Safety Set

AEs, Deaths, other serious adverse events or discontinuations due to AE, Part I (Safety set)

Outcome measures

Outcome measures
Measure	Canakinumab Dose Reduction n=68 Participants Cohort 1 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)	Canakinumab Dose Interval Prolongation n=98 Participants Cohort 2 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1 Number of patients with death	0 number of participants	0 number of participants
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1 Number of patients with at least one SAE	10 number of participants	23 number of participants
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 1 Number of patients with at least one AE	57 number of participants	91 number of participants

SECONDARY outcome

Timeframe: During study parts I and II, estimated study duration was not more than 216 weeks (with an average duration of 108 weeks).

Population: Safety Set

AEs, Deaths, other serious adverse events or discontinuations due to AE, Part II (Safety set)

Outcome measures

Outcome measures
Measure	Canakinumab Dose Reduction n=38 Participants Cohort 1 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)	Canakinumab Dose Interval Prolongation n=37 Participants Cohort 2 In total, 75 patients (Cohort 1: 56 and Cohort 2: 20) qualified for Study Part II and were randomized to receive canakinumab at either a reduced dose (n=38) or a prolonged dose interval (n=37)
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2 Number of patients with at least one AE	38 number of participants	34 number of participants
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2 Number of patients with death	0 number of participants	0 number of participants
Number and Percentage of Patients With Adverse Events as a Measure of Long-term Safety and Tolerability of Canakinumab - PART 2 Number of patients with at least one SAE	4 number of participants	1 number of participants

Adverse Events

Part I

Serious events: 33 serious events

Other events: 140 other events

Deaths: 0 deaths

Part II@Dose Reduction

Serious events: 4 serious events

Other events: 38 other events

Deaths: 0 deaths

Part II@Dose Interval@Prolongation

Serious events: 1 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Disclosure Office

Novartis Pharmaceuticals

Phone: +1 (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	Part I n=166 participants at risk Part I	Part II@Dose Reduction n=38 participants at risk Part II@Dose reduction	Part II@Dose Interval@Prolongation n=37 participants at risk Part II@Dose interval@prolongation
Blood and lymphatic system disorders Histiocytosis haematophagic	1.8% 3/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Blood and lymphatic system disorders Leukopenia	0.00% 0/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Blood and lymphatic system disorders Lymphadenitis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Blood and lymphatic system disorders Lymphadenopathy	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Cardiac disorders Pericarditis	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Eye disorders Eye swelling	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Abdominal pain	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Abdominal pain upper	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Diarrhoea	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Enteritis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
General disorders Pyrexia	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Appendicitis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Atypical pneumonia	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Bronchitis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Gastroenteritis	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Infectious mononucleosis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Influenza	0.00% 0/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Otitis media	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Otitis media acute	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Pneumonia	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Respiratory tract infection	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Viral infection	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Injury, poisoning and procedural complications Limb injury	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Arthritis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Juvenile idiopathic arthritis	4.8% 8/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Still's disease	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Nervous system disorders Idiopathic intracranial hypertension	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Renal and urinary disorders Nephrolithiasis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Respiratory, thoracic and mediastinal disorders Alveolar proteinosis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Lichen planus	0.00% 0/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Rash pruritic	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Rash scarlatiniform	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.

Other adverse events
Measure	Part I n=166 participants at risk Part I	Part II@Dose Reduction n=38 participants at risk Part II@Dose reduction	Part II@Dose Interval@Prolongation n=37 participants at risk Part II@Dose interval@prolongation
Blood and lymphatic system disorders Lymphadenopathy	6.0% 10/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Abdominal pain	7.8% 13/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.2% 5/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	16.2% 6/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Abdominal pain upper	8.4% 14/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Diarrhoea	10.8% 18/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	10.5% 4/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Nausea	6.6% 11/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Vomiting	10.2% 17/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
General disorders Injection site reaction	7.8% 13/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
General disorders Pyrexia	19.9% 33/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	23.7% 9/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	32.4% 12/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Bronchitis	5.4% 9/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.2% 5/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Gastroenteritis	7.2% 12/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.5% 5/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Influenza	9.6% 16/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.2% 5/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Nasopharyngitis	20.5% 34/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	26.3% 10/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	27.0% 10/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Pharyngitis	11.4% 19/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	16.2% 6/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Respiratory tract infection	9.6% 16/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Rhinitis	13.9% 23/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	10.5% 4/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	10.8% 4/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Tonsillitis	4.8% 8/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.5% 5/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Upper respiratory tract infection	13.9% 23/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	21.1% 8/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	16.2% 6/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Viral infection	5.4% 9/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.2% 5/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Metabolism and nutrition disorders Iron deficiency	6.0% 10/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Arthralgia	15.1% 25/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	21.1% 8/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	16.2% 6/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Back pain	5.4% 9/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Juvenile idiopathic arthritis	12.7% 21/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	15.8% 6/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	16.2% 6/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 9/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	18.9% 7/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Nervous system disorders Headache	15.7% 26/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.2% 5/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	18.9% 7/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Respiratory, thoracic and mediastinal disorders Cough	13.9% 23/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	23.7% 9/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.2% 17/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	15.8% 6/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	8.1% 3/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Eczema	9.0% 15/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Pruritus	4.8% 8/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Rash	9.6% 16/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	7.9% 3/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	13.5% 5/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Skin and subcutaneous tissue disorders Urticaria	5.4% 9/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Blood and lymphatic system disorders Leukopenia	4.2% 7/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Eye disorders Conjunctivitis allergic	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.6% 1/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Constipation	1.8% 3/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	10.5% 4/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Gastritis	0.60% 1/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	2.7% 1/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Odynophagia	0.00% 0/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Gastrointestinal disorders Toothache	1.8% 3/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
General disorders Fatigue	4.2% 7/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
General disorders Oedema peripheral	0.00% 0/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	0.00% 0/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Conjunctivitis	1.8% 3/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	10.8% 4/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.
Infections and infestations Cystitis	1.2% 2/166 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.3% 2/38 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.	5.4% 2/37 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to estimated study duration of not more than 216 weeks (with an average duration of 108 weeks) Arms/Groups are combined because a threshold of 5% indicates that all Other (Not Including Serious) Adverse Events with a frequency greater than 5% within at least one arm or comparison group are reported.