Trial Outcomes & Findings for A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration (NCT NCT03689972)

Last Updated: 2024-06-12

Results Overview

T2 hyperintense lesions were analyzed by magnetic resonance imaging (MRI) scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions at Week 72 relative to baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

585 participants

Primary outcome timeframe

Week 72

Results posted on

2024-06-12

Participant Flow

Participants were enrolled at the investigative sites in Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Spain, the United Kingdom, and the United States from 27 November 2018 to 20 June 2021.

585 participants were enrolled in the study, out of which 499 participants were randomized in Part 1. A total of 396 participants completed Part 1 of the study, out of which 67 participants entered Part 2 of the study. A total of 153 participants (including 86 new participants) entered Part 2 crossover period and 123 participants completed the study.

Participant milestones

Participant milestones
Measure	Part 1: Standard Interval Dosing (SID) (Every 4 Weeks [Q4W]) IV Participants received natalizumab 300 mg intravenous (IV) infusion Q4W up to Week 72.	Part 1: Extended Interval Dosing (EID) (Every 6 Weeks [Q6W]) IV Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.	Part 2: Run-in Period: IV Q6W Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.	Part 2: Crossover Period: IV Q6W Then SC Q6W Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg subcutaneous (SC) injection Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.	Part 2: Crossover Period: SC Q6W Then IV Q6W Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.
Part 1 (Day 1 up to Week 72) STARTED	248	251	0	0	0
Part 1 (Day 1 up to Week 72) COMPLETED	194	202	0	0	0
Part 1 (Day 1 up to Week 72) NOT COMPLETED	54	49	0	0	0
Part 2:Run-in Period (Week73uptoWeek107) STARTED	0	0	158	0	0
Part 2:Run-in Period (Week73uptoWeek107) COMPLETED	0	0	153	0	0
Part 2:Run-in Period (Week73uptoWeek107) NOT COMPLETED	0	0	5	0	0
Part2CrossoverPeriod(Week108uptoWeek156) STARTED	0	0	0	75	78
Part2CrossoverPeriod(Week108uptoWeek156) COMPLETED	0	0	0	63	60
Part2CrossoverPeriod(Week108uptoWeek156) NOT COMPLETED	0	0	0	12	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Standard Interval Dosing (SID) (Every 4 Weeks [Q4W]) IV Participants received natalizumab 300 mg intravenous (IV) infusion Q4W up to Week 72.	Part 1: Extended Interval Dosing (EID) (Every 6 Weeks [Q6W]) IV Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.	Part 2: Run-in Period: IV Q6W Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.	Part 2: Crossover Period: IV Q6W Then SC Q6W Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg subcutaneous (SC) injection Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.	Part 2: Crossover Period: SC Q6W Then IV Q6W Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.
Part 1 (Day 1 up to Week 72) Adverse Event	1	3	0	0	0
Part 1 (Day 1 up to Week 72) Lost to Follow-up	0	2	0	0	0
Part 1 (Day 1 up to Week 72) Protocol-Defined Rescue Criteria	0	6	0	0	0
Part 1 (Day 1 up to Week 72) Developed Persistent Anti-Natalizumab Antibodies	1	3	0	0	0
Part 1 (Day 1 up to Week 72) Consent Withdrawn	14	9	0	0	0
Part 1 (Day 1 up to Week 72) Investigator Decision	9	6	0	0	0
Part 1 (Day 1 up to Week 72) Pregnancy	5	1	0	0	0
Part 1 (Day 1 up to Week 72) Unwilling to Comply With Protocol	3	2	0	0	0
Part 1 (Day 1 up to Week 72) Randomized but not Dosed	1	1	0	0	0
Part 1 (Day 1 up to Week 72) Reason not Specified	20	16	0	0	0
Part 2:Run-in Period (Week73uptoWeek107) Consent Withdrawn	0	0	2	0	0
Part 2:Run-in Period (Week73uptoWeek107) Pregnancy	0	0	1	0	0
Part 2:Run-in Period (Week73uptoWeek107) Reason not Specified	0	0	2	0	0
Part2CrossoverPeriod(Week108uptoWeek156) Adverse Event	0	0	0	1	1
Part2CrossoverPeriod(Week108uptoWeek156) Consent Withdrawn	0	0	0	7	1
Part2CrossoverPeriod(Week108uptoWeek156) Investigator Decision	0	0	0	2	2
Part2CrossoverPeriod(Week108uptoWeek156) Pregnancy	0	0	0	0	1
Part2CrossoverPeriod(Week108uptoWeek156) Reason not Specified	0	0	0	2	1
Part2CrossoverPeriod(Week108uptoWeek156) Randomized but not Dosed	0	0	0	0	12

Baseline Characteristics

A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: IV Q4W n=248 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=251 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.	Part 2: Crossover Period n=86 Participants Participants who were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg SC injection Q6W from Week 132 through Week 150, or natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150, along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.	Total n=585 Participants Total of all reporting groups
Age, Continuous	40.5 Years STANDARD_DEVIATION 10.03 • n=5 Participants	41.0 Years STANDARD_DEVIATION 9.66 • n=7 Participants	37.6 Years STANDARD_DEVIATION 9.85 • n=5 Participants	40.3 Years STANDARD_DEVIATION 9.9 • n=4 Participants
Sex: Female, Male Female	181 Participants n=5 Participants	178 Participants n=7 Participants	58 Participants n=5 Participants	417 Participants n=4 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	73 Participants n=7 Participants	28 Participants n=5 Participants	168 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	223 Participants n=5 Participants	224 Participants n=7 Participants	67 Participants n=5 Participants	514 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	51 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	23 Participants n=5 Participants	14 Participants n=7 Participants	0 Participants n=5 Participants	37 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	211 Participants n=5 Participants	211 Participants n=7 Participants	71 Participants n=5 Participants	493 Participants n=4 Participants
Race/Ethnicity, Customized Race · Not Reported	11 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	40 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 72

Population: Modified intent to treat (mITT) population included all randomized participants who received at least one dose of study treatment and had at least one postbaseline result in Part 1. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=197 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=211 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72	0.05 number of T2 lesions Interval 0.01 to 0.22	0.20 number of T2 lesions Interval 0.07 to 0.63

PRIMARY outcome

Timeframe: Week 150

Population: mITT population included all randomized participants who received at least one dose of SC natalizumab after randomization in Part 2 and who completed at least the first question in the Patient Preference Questionnaire (PPQ) on one occasion. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. (Confidence interval=CI)

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=62 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=61 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Crossover Period of Part 2	83.9 percentage of participants	91.8 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 72

Population: mITT population included all randomized participants who received at least one dose of study treatment and had at least one postbaseline result in Part 1.

Relapse is defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC were included in the analysis. Time to First Relapse was estimated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=242 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=247 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)	NA weeks Median, Q1 and Q3 were not reached in the Kaplan-Meier curve due to insufficient number of relapses.	NA weeks Median, Q1 and Q3 were not reached in the Kaplan-Meier curve due to insufficient number of relapses.

SECONDARY outcome

Timeframe: Week 72

Population: mITT population included all randomized participants who received at least one dose of study treatment and had at least one postbaseline result in Part 1.

Annualized relapse rate is calculated as the total number of INEC-confirmed relapses that occurred during the treatment period divided by the total number of participant-years followed in the period.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=242 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=247 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Annualized Relapse Rate at Week 72	0.00010 relapses per participant-year Interval 0.00004 to 0.00024	0.0001 relapses per participant-year Interval 0.00006 to 0.00027

SECONDARY outcome

Timeframe: Up to Week 72

Population: mITT population included all randomized participants who received at least one dose of study treatment and had at least one postbaseline result in Part 1.

Confirmed EDSS worsening is defined as an increase of at least 1.0 point from a baseline EDSS score ≥ 1.0 or an increase of at least 1.5 points from a baseline EDSS score of 0 that is confirmed after at least 24 weeks. Time to EDSS worsening is estimated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=242 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=247 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening	NA weeks Median, Q1, and Q3 were not reached in the Kaplan-Meier curve due to insufficient number of events.	NA weeks Median, Q1, and Q3 were not reached in the Kaplan-Meier curve due to insufficient number of events.

SECONDARY outcome

Timeframe: Weeks 24, 48, and 72

Population: mITT population included all randomized participants who received at least one dose of study treatment and had at least one postbaseline result in Part 1. 'Overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. Here, 'number analyzed' signifies the number of participants with data available for analysis at specified time-point.

T1 hypointense lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new T1 hypointense lesions at Weeks 24, 48, and 72 relative to baseline.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=227 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=241 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72 Week 24	0.0 number of T1 lesions Standard Deviation 0.13	0.0 number of T1 lesions Standard Deviation 0.06
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72 Week 48	0.0 number of T1 lesions Standard Deviation 0.16	0.0 number of T1 lesions Standard Deviation 0.07
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72 Week 72	0.0 number of T1 lesions Standard Deviation 0.16	0.0 number of T1 lesions Standard Deviation 0.32

SECONDARY outcome

Timeframe: Weeks 24 and 48

T2 hyperintense lesions were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions at Weeks 24 and 48 relative to baseline.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=229 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=242 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48 Week 24	0.0 number of T2 lesions Standard Deviation 0.16	0.0 number of T2 lesions Standard Deviation 0.35
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48 Week 48	0.0 number of T2 lesions Standard Deviation 0.21	0.1 number of T2 lesions Standard Deviation 1.03

SECONDARY outcome

Timeframe: Weeks 24, 48, and 72

Gd enhancing lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new Gd enhancing lesions at Weeks 24, 48, and 72 relative to baseline.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=227 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=241 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72 Week 24	0.0 number of Gd lesions Standard Deviation 0.07	0.0 number of Gd lesions Standard Deviation 0.00
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72 Week 48	0.0 number of Gd lesions Standard Deviation 0.07	0.0 number of Gd lesions Standard Deviation 0.00
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72 Week 72	0.0 number of Gd lesions Standard Deviation 0.07	0.1 number of Gd lesions Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline up to Week 84

Population: Safety population included all randomized participants who received at least one dose of study treatment in Part 1.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any event occurring on or after first dose after randomization up to 12 weeks (or 24 weeks for PML \[progressive multifocal leukoencephalopathy\] events) following the last dose on the study.An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=247 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=250 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	76.9 percentage of participants	77.6 percentage of participants
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	6.9 percentage of participants	6.8 percentage of participants

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Population: Full analysis set included all randomized participants who received at least one dose of study treatment during at least one study period and had at least one baseline assessment in Part 2. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.

The TSQM has 14 questions that assesses participants' global satisfaction level with their treatment in 4 domains: side effects (There are 5 questions in the side effects domain, however one of them is a Yes/No question and there are 4 sub-components, hence a maximum score of 20), effectiveness (3 questions), global satisfaction (3 questions), and convenience (3 questions). All questions are scored from 1 (least satisfied) to 5 or 7 (most satisfied). The total score is summed for each domain to obtain: side effects (1-20), effectiveness (1-21), global satisfaction (1-17), and convenience (1-21), using transformed scores between 0 and 100 for effectiveness. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=127 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=127 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores During the Crossover Period	0.17 Score on a scale Standard Error 0.899	0.64 Score on a scale Standard Error 0.902

SECONDARY outcome

Timeframe: Week 108 up to Week 156

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=136 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period Drug Preparation Time	4.9 minutes Standard Deviation 3.86	0 minutes Standard Deviation 0
Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period Drug Administration Time	62.6 minutes Standard Deviation 10.45	4.3 minutes Standard Deviation 5.11

SECONDARY outcome

Timeframe: Part 2: Baseline (Week 108) up to Week 180

Population: Safety population included all randomized participants who received at least one dose of study treatment during the crossover period of Part 2.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=136 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	57.4 percentage of participants	62.9 percentage of participants

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Population: Immunogenicity population included all participants who received at least one dose of SC or IV natalizumab and had at least one assessment for anti-drug antibody during crossover period of Part 2.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=136 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Percentage of Participants With Anti-Natalizumab Antibodies During the Crossover Period	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=131 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=128 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions During the Crossover Period	0.0 number of T2 lesions Standard Deviation 0.09	0.0 number of T2 lesions Standard Deviation 0.22

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Population: FAS: all randomized participants receiving ≥1 dose of study treatment during at least one study period and had ≥1 baseline assessment in Part 2. Overall number analyzed: participants without any relapse at beginning of crossover period of Part 2. As pre-specified in the Statistical Analysis Plan(SAP), time to event analyses was planned 'per treatment sequence' rather than 'per intervention' in Part 2 as protocol-specified analysis does not account for correlation of within participant effect.

Relapse is defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours. The time to first relapse is defined as the time from the first randomized dose in Part 2 up to the first relapse. Time to First Relapse is estimated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=71 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=63 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Time to First Relapse During the Crossover Period	NA weeks Median, Q1, and Q3 were not reached in the Kaplan-Meier curve due to one relapse.	NA weeks Data is not available as no participant in this group had a relapse.

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Population: Data was not analyzed for this outcome measure as only one relapse was observed in the Part 2 crossover period.

Annualized relapse rate is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years followed in the period.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=135 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Change From Baseline in EDSS Score During the Crossover Period	0.02 Score on a scale Standard Error 0.055	0.10 Score on a scale Standard Error 0.056

SECONDARY outcome

Timeframe: Week 108 up to Week 156

Gd enhancing lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new Gd enhancing lesions during the crossover period of Part 2 relative to baseline.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=131 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=128 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Number of New Gd Enhancing Lesions During the Crossover Period	0.0 number of Gd lesions Standard Deviation 0.00	0.0 number of Gd lesions Standard Deviation 0.00

SECONDARY outcome

Timeframe: Week 108 up to Week 156

T1 hypointense lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new T1 hypointense lesions during the crossover period of Part 2 relative to baseline.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=131 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=128 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Number of New T1 Hypointense Lesions During the Crossover Period	0.0 number of T1 lesions Standard Deviation 0.09	0.0 number of T1 lesions Standard Deviation 0.00

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=112 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=108 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Percentage Change From Baseline in Brain Volume During the Crossover Period	-0.11 percent change Standard Error 0.042	-0.10 percent change Standard Error 0.042

SECONDARY outcome

Timeframe: Part 2 Baseline (Week 108) up to Week 156

Population: Full analysis set included all randomized participants who received at least one dose of study treatment during at least one study period and had at least one baseline assessment in Part 2. 'Overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis. Here "number analyzed" signifies the number of participants with data available for analysis at specified categories.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=111 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=107 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period Cortical Brain Region	-1478.82 cubic centimeters (cm^3) Standard Error 363.714	-881.34 cubic centimeters (cm^3) Standard Error 367.155
Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period Thalamic Brain Region	-25.98 cubic centimeters (cm^3) Standard Error 14.582	-17.96 cubic centimeters (cm^3) Standard Error 14.796

SECONDARY outcome

Timeframe: Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156

Population: Pharmacokinetic (PK) population included all participants who received at least one dose of SC or IV natalizumab and had at least one assessment for the concentration of natalizumab in serum during the crossover period of Part 2.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=136 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Trough Serum Concentration of Natalizumab (Ctrough) During the Crossover Period	11.9 micrograms per milliliter (µg/mL) Standard Deviation 11.50	10.3 micrograms per milliliter (µg/mL) Standard Deviation 10.94

SECONDARY outcome

Timeframe: Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156

Population: Pharmacodynamic (PD) population included all participants who received at least one dose of SC or IV natalizumab after randomization in Part 2 and had at least one post-baseline assessment of the PD parameter. Here 'overall number of participants analyzed' indicates the number of participants without any relapse at the beginning of the crossover period of Part 2.

Outcome measures

Outcome measures
Measure	Part 1: IV Q4W n=135 Participants Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=132 Participants Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.
Part 2: Mean Trough α4 Integrin Saturation During the Crossover Period	71.2 percentage Standard Deviation 15.31	67.2 percentage Standard Deviation 17.80

Adverse Events

Part 1: IV Q4W

Serious events: 17 serious events

Other events: 104 other events

Deaths: 0 deaths

Part 1: IV Q6W

Serious events: 17 serious events

Other events: 105 other events

Deaths: 0 deaths

Part 2: Run-in Period: IV Q6W

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

Part 2: Crossover Period: IV Q6W

Serious events: 2 serious events

Other events: 48 other events

Deaths: 0 deaths

Part 2: Crossover Period: SC Q6W

Serious events: 4 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1: IV Q4W n=247 participants at risk Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=250 participants at risk Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.	Part 2: Run-in Period: IV Q6W n=158 participants at risk Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.	Part 2: Crossover Period: IV Q6W n=136 participants at risk Participants received natalizumab 300 mg IV infusion Q6W for 24 weeks.	Part 2: Crossover Period: SC Q6W n=132 participants at risk Participants received natalizumab 300 mg SC injection Q6W for 24 weeks.
Psychiatric disorders Depression	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Psychiatric disorders Suicidal ideation	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Blood and lymphatic system disorders Anaemia	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Cardiac disorders Coronary artery dissection	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Endocrine disorders Goitre	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Eye disorders Papilloedema	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Gastrointestinal disorders Diarrhoea	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Gastrointestinal disorders Hiatus hernia	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.74% 1/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Hepatobiliary disorders Cholecystitis	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Hepatobiliary disorders Cholelithiasis	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.80% 2/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Immune system disorders Drug hypersensitivity	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Cholangitis infective	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Covid-19 pneumonia	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Gastroenteritis	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Herpes zoster	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Pneumonia	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Progressive multifocal leukoencephalopathy	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Respiratory tract infection	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Fall	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Humerus fracture	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Respiratory tract procedural complication	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Metabolism and nutrition disorders Dehydration	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign lung neoplasm	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.74% 1/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Hemiparesis	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Lumbar radiculopathy	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Lumbosacral radiculopathy	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Migraine	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Multiple sclerosis pseudo relapse	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Neuropathy peripheral	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Optic neuritis	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Pregnancy, puerperium and perinatal conditions Abortion	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Psychiatric disorders Suicide attempt	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Renal and urinary disorders Renal colic	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Renal and urinary disorders Ureterolithiasis	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Reproductive system and breast disorders Adnexal torsion	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Reproductive system and breast disorders Endometriosis	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.40% 1/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Vascular disorders Venous thrombosis limb	0.40% 1/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.00% 0/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.

Other adverse events

Other adverse events
Measure	Part 1: IV Q4W n=247 participants at risk Participants received natalizumab 300 mg IV infusion Q4W up to Week 72.	Part 1: IV Q6W n=250 participants at risk Participants received natalizumab 300 mg IV infusion Q6W up to Week 72.	Part 2: Run-in Period: IV Q6W n=158 participants at risk Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.	Part 2: Crossover Period: IV Q6W n=136 participants at risk Participants received natalizumab 300 mg IV infusion Q6W for 24 weeks.	Part 2: Crossover Period: SC Q6W n=132 participants at risk Participants received natalizumab 300 mg SC injection Q6W for 24 weeks.
General disorders Fatigue	3.2% 8/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	10.0% 25/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.5% 4/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.2% 3/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Covid-19	2.4% 6/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.0% 5/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	12.0% 19/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	20.6% 28/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	23.5% 31/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Nasopharyngitis	13.0% 32/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	10.8% 27/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.5% 4/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.2% 3/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	9.8% 13/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Upper respiratory tract infection	6.9% 17/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	4.8% 12/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	3.0% 4/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Infections and infestations Urinary tract infection	7.7% 19/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	9.6% 24/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	3.8% 6/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	5.1% 7/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Injury, poisoning and procedural complications Fall	5.3% 13/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	5.2% 13/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	3.2% 5/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Musculoskeletal and connective tissue disorders Arthralgia	3.6% 9/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	7.2% 18/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.63% 1/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	6.1% 8/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Musculoskeletal and connective tissue disorders Pain in extremity	2.8% 7/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	5.6% 14/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.5% 4/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.74% 1/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Nervous system disorders Headache	9.3% 23/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	10.4% 26/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.5% 4/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	5.1% 7/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	3.0% 4/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.
Respiratory, thoracic and mediastinal disorders Cough	1.6% 4/247 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	5.6% 14/250 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	2.5% 4/158 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	1.5% 2/136 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.	0.76% 1/132 • From first dose of study drug up to Week 180 Safety population included all randomized participants who received at least one dose of study treatment. MedDRA version 24.0 applied for Part 1 and MedDRA version 26.0 applied for Part 2.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER