Trial Outcomes & Findings for A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis (NCT NCT00050778)

Last Updated: 2015-01-08

Results Overview

EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

334 participants

Primary outcome timeframe

Up to 3 years

Results posted on

2015-01-08

Participant Flow

The study was conducted at 49 investigational sites in the United States, United Kingdom, and Eastern Europe between December 04, 2002 and January 12, 2010.

Participant milestones

Participant milestones
Measure	Interferon Beta-1a Interferon beta-1a (Rebif®) 44 micrograms (mcg) subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg Alemtuzumab (Lemtrada™) 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ \[CD4+\] T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Overall Study STARTED	111	113	110
Overall Study Treated	107	108	108
Overall Study COMPLETED	66	92	92
Overall Study NOT COMPLETED	45	21	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Interferon Beta-1a Interferon beta-1a (Rebif®) 44 micrograms (mcg) subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg Alemtuzumab (Lemtrada™) 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ \[CD4+\] T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Overall Study Adverse Event	13	3	2
Overall Study Death	0	1	1
Overall Study Lack of Efficacy	16	2	2
Overall Study Lost to Follow-up	0	2	4
Overall Study Physician Decision	3	0	2
Overall Study Protocol Violation	2	0	1
Overall Study Withdrawal by Subject	6	8	4
Overall Study Randomized but not treated	4	5	2
Overall Study Familial and personal reasons	1	0	0

Baseline Characteristics

A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Interferon Beta-1a n=111 Participants Interferon beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=112 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=110 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Total n=333 Participants Total of all reporting groups
Age, Continuous	32.8 years STANDARD_DEVIATION 8.82 • n=5 Participants	31.9 years STANDARD_DEVIATION 8.01 • n=7 Participants	32.2 years STANDARD_DEVIATION 8.76 • n=5 Participants	32.3 years STANDARD_DEVIATION 8.52 • n=4 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	72 Participants n=7 Participants	71 Participants n=5 Participants	214 Participants n=4 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	40 Participants n=7 Participants	39 Participants n=5 Participants	119 Participants n=4 Participants
Time Since First Relapse	1.4 years n=5 Participants	1.3 years n=7 Participants	1.2 years n=5 Participants	1.3 years n=4 Participants
Number of Relapse Episodes in the Preceding 2 Years 0 Relapse	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Number of Relapse Episodes in the Preceding 2 Years 1 Relapse	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants	26 participants n=4 Participants
Number of Relapse Episodes in the Preceding 2 Years 2 Relapses	73 participants n=5 Participants	58 participants n=7 Participants	56 participants n=5 Participants	187 participants n=4 Participants
Number of Relapse Episodes in the Preceding 2 Years Greater than or equal to 3 Relapses	30 participants n=5 Participants	47 participants n=7 Participants	40 participants n=5 Participants	117 participants n=4 Participants
Total Number of Relapses	293 relapses n=5 Participants	301 relapses n=7 Participants	290 relapses n=5 Participants	884 relapses n=4 Participants
Expanded Disability Status Scale (EDSS) Score	1.9 units on a scale STANDARD_DEVIATION 0.81 • n=5 Participants	2.0 units on a scale STANDARD_DEVIATION 0.73 • n=7 Participants	2.0 units on a scale STANDARD_DEVIATION 0.73 • n=5 Participants	1.9 units on a scale STANDARD_DEVIATION 0.76 • n=4 Participants
Time Constant 1 (T1) Cerebral Volume	317.5 cubic centimeter STANDARD_DEVIATION 24.70 • n=5 Participants	320.8 cubic centimeter STANDARD_DEVIATION 27.15 • n=7 Participants	320.5 cubic centimeter STANDARD_DEVIATION 24.99 • n=5 Participants	319.6 cubic centimeter STANDARD_DEVIATION 25.61 • n=4 Participants
Time Constant 2 (T2) Lesion Volume	15.8 cubic centimeter STANDARD_DEVIATION 15.23 • n=5 Participants	17.2 cubic centimeter STANDARD_DEVIATION 23.84 • n=7 Participants	17.8 cubic centimeter STANDARD_DEVIATION 17.45 • n=5 Participants	17.0 cubic centimeter STANDARD_DEVIATION 19.19 • n=4 Participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: Full Analysis Set (FAS) population included all randomized participants who had correct diagnosis of MS at entry.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a n=111 Participants Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=112 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=110 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=222 Participants Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Probability of Participants With Sustained Accumulation of Disability (SAD)	0.27 probability of participants with SAD Interval 0.193 to 0.38	0.08 probability of participants with SAD Interval 0.043 to 0.165	0.09 probability of participants with SAD Interval 0.052 to 0.169	0.09 probability of participants with SAD Interval 0.057 to 0.139

PRIMARY outcome

Timeframe: Up to 3 years

Population: FAS population included all randomized participants who had correct diagnosis of MS at entry.

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a n=111 Participants Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=112 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=110 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=222 Participants Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Annualized Relapse Rate	0.37 relapses per participant per year Interval 0.297 to 0.449	0.12 relapses per participant per year Interval 0.091 to 0.171	0.09 relapses per participant per year Interval 0.064 to 0.133	0.11 relapses per participant per year Interval 0.085 to 0.137

SECONDARY outcome

Timeframe: Year 3

Population: FAS population included all randomized participants who had correct diagnosis of MS at entry.

Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.

Outcome measures

Outcome measures
Measure	Interferon Beta-1a n=111 Participants Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=112 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=110 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=222 Participants Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment	0.50 probability of participants Interval 0.395 to 0.602	0.76 probability of participants Interval 0.667 to 0.832	0.84 probability of participants Interval 0.748 to 0.894	0.80 probability of participants Interval 0.737 to 0.847

SECONDARY outcome

Timeframe: Baseline, Year 3

Population: Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T1 brain volume at Baseline and Year 3.

Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100\*(\[brain volume at Year 3\] minus \[brain volume at Baseline\]) divided by \[brain volume at Baseline\]).

Outcome measures

Outcome measures
Measure	Interferon Beta-1a n=67 Participants Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=83 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=90 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=173 Participants Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Percent Change From Baseline in T1 Cerebral Volume at Year 3	-1.9 percent change Standard Deviation 4.48	-0.8 percent change Standard Deviation 3.66	-0.4 percent change Standard Deviation 4.27	-0.6 percent change Standard Deviation 3.99

SECONDARY outcome

Timeframe: Baseline, Year 3

Population: Analysis population included participants in the FAS population (randomized with a correct diagnosis of MS) who had an evaluable scan for MRI-T2 lesion volume at Baseline and Year 3.

Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100\*(\[lesion volume at Year 3\] minus \[lesion volume at Baseline\]) divided by \[lesion volume at Baseline\]).

Outcome measures

Outcome measures
Measure	Interferon Beta-1a n=66 Participants Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=81 Participants Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=88 Participants Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=169 Participants Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Percent Change From Baseline in MRI T2 Lesion Volume at Year 3	23.4 percent change Standard Deviation 134.3	-11.4 percent change Standard Deviation 38.8	-8.9 percent change Standard Deviation 41.1	-10.1 percent change Standard Deviation 39.9

Adverse Events

Interferon Beta-1a

Serious events: 29 serious events

Other events: 106 other events

Deaths: 0 deaths

Alemtuzumab 12 mg

Serious events: 30 serious events

Other events: 108 other events

Deaths: 0 deaths

Alemtuzumab 24 mg

Serious events: 33 serious events

Other events: 108 other events

Deaths: 0 deaths

Alemtuzumab (Pooled)

Serious events: 63 serious events

Other events: 216 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In multi-site studies, PI can publish after sponsor publishes or 18 months after study completion. PI gives sponsor a draft 60 days before publication. Sponsor can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Interferon Beta-1a n=107 participants at risk Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=108 participants at risk Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=108 participants at risk Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=216 participants at risk Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Gastrointestinal disorders Ileus paralytic	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Blood and lymphatic system disorders Autoimmune thrombocytopenia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 2/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 2/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Angina pectoris	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Arrhythmia	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Bradycardia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Cardiovascular disorder	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Myocardial infarction	2.8% 3/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Pericarditis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Autoimmune thyroiditis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Basedow's disease	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 2/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Thyroiditis subacute	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Cataract	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Diplopia	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Exophthalmos	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Vision blurred	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Visual acuity reduced	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Abdominal hernia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Enterocutaneous fistula	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Erosive oesophagitis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Gastric ulcer	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 2/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Gastroduodenitis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Hypoaesthesia oral	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Ileus	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Nausea	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Paraesthesia oral	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Peritonitis	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Salivary gland calculus	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Vomiting	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Adverse drug reaction	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Asthenia	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Chest discomfort	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Death	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Fatigue	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.

Other adverse events
Measure	Interferon Beta-1a n=107 participants at risk Interferon Beta-1a 44 mcg subcutaneously 3-times weekly for 36 months.	Alemtuzumab 12 mg n=108 participants at risk Alemtuzumab 12 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab 24 mg n=108 participants at risk Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).	Alemtuzumab (Pooled) n=216 participants at risk Included all participants who received alemtuzumab 12 mg/day or 24 mg/day by intravenous infusion on 5 consecutive days during first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was \>=100\*10\^6 cells per liter).
Blood and lymphatic system disorders Neutropenia	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	3.7% 4/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.6% 10/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Palpitations	2.8% 3/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	7.4% 8/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.5% 14/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Cardiac disorders Tachycardia	5.6% 6/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 13/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 13/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 26/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Ear and labyrinth disorders Vertigo	9.3% 10/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.1% 12/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 11/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.6% 23/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Basedow's disease	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.1% 12/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 18/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Hyperthyroidism	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 11/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 13/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.1% 24/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Endocrine disorders Hypothyroidism	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 11/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 11/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 22/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Diplopia	6.5% 7/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 3/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.2% 9/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Vision blurred	3.7% 4/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	14.8% 16/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.6% 25/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Eye disorders Visual acuity reduced	5.6% 6/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	3.7% 4/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 6/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Abdominal pain	6.5% 7/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.6% 5/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.1% 11/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Abdominal pain upper	5.6% 6/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	3.7% 4/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 6/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Constipation	8.4% 9/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.9% 15/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Diarrhoea	6.5% 7/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	15.7% 17/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	15.7% 17/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	15.7% 34/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Oral herpes	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.5% 7/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	7.4% 8/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.9% 15/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Dyspepsia	8.4% 9/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	14.8% 16/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 13/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.4% 29/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.5% 7/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.0% 13/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Nausea	15.9% 17/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	29.6% 32/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	41.7% 45/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	35.6% 77/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Stomatitis	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.9% 2/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.1% 11/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Toothache	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	3.2% 7/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Gastrointestinal disorders Vomiting	8.4% 9/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	16.7% 18/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	17.6% 19/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	17.1% 37/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Asthenia	4.7% 5/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	16.7% 18/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.1% 12/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.9% 30/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Chest discomfort	2.8% 3/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.1% 12/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	16.7% 18/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.9% 30/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Chills	7.5% 8/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	17.6% 19/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	19.4% 21/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	18.5% 40/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Fatigue	29.0% 31/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	43.5% 47/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	40.7% 44/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	42.1% 91/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Gait disturbance	12.1% 13/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.6% 5/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.1% 11/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Hyperthermia	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.5% 7/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.6% 5/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 12/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Influenza like illness	29.9% 32/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	19.4% 21/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.9% 15/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	16.7% 36/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Injection site erythema	32.7% 35/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Injection site pain	16.8% 18/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 3/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	1.4% 3/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Injection site reaction	11.2% 12/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.93% 1/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.00% 0/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	0.46% 1/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Oedema peripheral	3.7% 4/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 6/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 3/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	4.2% 9/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Pain	5.6% 6/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.0% 13/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.0% 14/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	12.5% 27/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
General disorders Pyrexia	10.3% 11/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	43.5% 47/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	43.5% 47/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	43.5% 94/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Bronchitis	2.8% 3/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	10.2% 11/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	13.0% 14/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	11.6% 25/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Herpes zoster	0.93% 1/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	3.7% 4/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	7.4% 8/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 12/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Influenza	3.7% 4/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	9.3% 10/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 3/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	6.0% 13/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Nasopharyngitis	13.1% 14/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	15.7% 17/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	24.1% 26/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	19.9% 43/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Pharyngitis	3.7% 4/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	2.8% 3/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	5.6% 12/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.
Infections and infestations Rhinitis	2.8% 3/107 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 9/108 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.	8.3% 18/216 • First dose of study drug up to last follow-up (80.6 months) If a participant experienced both a serious and a non-serious event with the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. The analysis was performed on the safety population, defined as all participants who received any amount of study drug.