Trial Outcomes & Findings for Natalizumab (BG00002, Tysabri) Study in Japanese Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) (NCT NCT01440101)

Last Updated: 2014-10-21

Results Overview

AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. Serious AE (SAE)=any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, was a life threatening event; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or any other medically important event that, in the opinion of the Investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as related or not related; severity was categorized as mild, moderate, or severe.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

106 participants

Primary outcome timeframe

Baseline (Week 0) to Week 24

Results posted on

2014-10-21

Participant Flow

This was a 2-part, multicenter study, each part (open-label, double-blind) comprising discrete cohorts of BG00002-naïve participants.

Participant milestones

Participant milestones
Measure	Open Label Natalizumab 300 mg intravenous (IV) infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Placebo IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Overall Study STARTED	12	47	47
Overall Study COMPLETED	10	43	46
Overall Study NOT COMPLETED	2	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Open Label Natalizumab 300 mg intravenous (IV) infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Placebo IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Overall Study Adverse Event	2	0	0
Overall Study Withdrawal by Subject	0	3	1
Overall Study Other	0	1	0

Baseline Characteristics

Natalizumab (BG00002, Tysabri) Study in Japanese Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Placebo n=47 Participants IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Total n=106 Participants Total of all reporting groups
Age, Customized 18 to < 20 years	0 participants n=99 Participants	2 participants n=107 Participants	0 participants n=206 Participants	2 participants n=7 Participants
Age, Customized 20 to < 30 years	1 participants n=99 Participants	8 participants n=107 Participants	9 participants n=206 Participants	18 participants n=7 Participants
Age, Customized 30 to < 40 years	6 participants n=99 Participants	24 participants n=107 Participants	18 participants n=206 Participants	48 participants n=7 Participants
Age, Customized 40 to < 50 years	3 participants n=99 Participants	10 participants n=107 Participants	16 participants n=206 Participants	29 participants n=7 Participants
Age, Customized 50 to < 60 years	1 participants n=99 Participants	3 participants n=107 Participants	3 participants n=206 Participants	7 participants n=7 Participants
Age, Customized >/= 60 years	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants	2 participants n=7 Participants
Sex: Female, Male Female	7 Participants n=99 Participants	32 Participants n=107 Participants	34 Participants n=206 Participants	73 Participants n=7 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	15 Participants n=107 Participants	13 Participants n=206 Participants	33 Participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 24

Population: All participants who received study drug.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Number of Participants With Adverse Events (AEs) Participants with an adverse event (AE)	8 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants with a moderate or severe event	4 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants with a severe event	1 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants with an AE related to study drug	3 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants with a serious event (SAE)	2 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants with an SAE related to study drug	1 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants discontinuing treatment due to an AE	1 participants	—
Part A: Number of Participants With Adverse Events (AEs) Participants withdrawing from study due to an AE	2 participants	—

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 24

Population: Missing new Gd+ or new or newly-enlarging, non-enhancing T2 hyperintense lesions were imputed using linear interpolation between the 2 adjacent non-missing values. For participants who discontinued the study, linear interpolation reduced to last observation carried forward (LOCF) was used for imputing any remaining missing values.

New active lesions were the sum of the gadolinium-enhancing (Gd+) lesions and any new or newly enlarging T2 hyperintense lesions that did not enhance as seen on cranial magnetic resonance imaging (MRI) scans. The rate is calculated for each participant as the ordinary least squares slope of the cumulative new active lesions over time.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Rate of Development of New Active Lesions Over 24 Weeks	0.352 lesions per week over 24 weeks Standard Deviation 0.5648	0.058 lesions per week over 24 weeks Standard Deviation 0.0748

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Cumulative Number of New Active Lesions Over 24 Weeks	8.5 lesions Standard Deviation 13.35	1.5 lesions Standard Deviation 2.06

SECONDARY outcome

Timeframe: Week 24

The frequency of clinical exacerbations over 24 weeks was assessed using an annualized relapse rate that was calculated for each treatment group as the total number of relapses experienced in the group over the 24 weeks of treatment, divided by the total number of subject-years followed in the study. Obtained from a Poisson regression model, adjusted for the baseline relapse rate.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=27 Participants with Relapse 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=9 Participants with Relapse 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Adjusted Annualized Relapse Rate Over 24 Weeks	1.727 relapses per year Interval 1.218 to 2.448	0.532 relapses per year Interval 0.286 to 0.992

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Cumulative Number of Gd+ Lesions Over 24 Weeks	7.4 lesions Standard Deviation 12.15	1.2 lesions Standard Deviation 1.68

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Cumulative Number Of New Or Newly Enlarging, Non-Enhancing T2-Hyperintense Lesions Over 24 Weeks	1.1 lesions Standard Deviation 1.84	0.3 lesions Standard Deviation 0.91

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24

Population: All participants who received study drug.

Participants were categorized as relapse free=yes, relapse free=no, or relapse free=unknown. The category of relapse free=unknown includes participants who withdrew from the study and did not experience a relapse prior to withdrawal.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Number of Participants Who Were Relapse Free Over 24 Weeks Relapse free = yes	18 participants	37 participants
Part B: Number of Participants Who Were Relapse Free Over 24 Weeks Relapse free = no	27 participants	9 participants
Part B: Number of Participants Who Were Relapse Free Over 24 Weeks Relapse free = unknown	2 participants	1 participants

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, Week 24

Population: n = all participants with an assessment at baseline and given timepoint.

The participant's self-rating of global impression of his/her well-being was assessed with a VAS. The instrument ranged from 0 to 100 (mm), where a score of 0 denoted 'poor' and a score of 100 denoted 'excellent.'

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Change From Baseline to Weeks 12 and 24 in the Global Assessment of Well-Being As Assessed by Participants Using a Visual Analog Scale (VAS) Baseline; n=47, 47	63.5 units on a scale Standard Deviation 23.66	69.6 units on a scale Standard Deviation 20.70
Part B: Change From Baseline to Weeks 12 and 24 in the Global Assessment of Well-Being As Assessed by Participants Using a Visual Analog Scale (VAS) Change from Baseline at Week 12; n=47, 47	-4.9 units on a scale Standard Deviation 24.89	-5.3 units on a scale Standard Deviation 21.49
Part B: Change From Baseline to Weeks 12 and 24 in the Global Assessment of Well-Being As Assessed by Participants Using a Visual Analog Scale (VAS) Change from Baseline at Week 24; n=44, 46	-2.9 units on a scale Standard Deviation 25.20	-4.8 units on a scale Standard Deviation 17.40

SECONDARY outcome

Timeframe: Week 0: pre-dose, post-dose and 2, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose; Weeks 4, 8, 12, and 16: pre-dose; Week 20 pre-dose, post-dose, and 2, 24, 48 and 96 hours post-dose; 7, 14, 21, and 28 days post-dose

Population: Participants who received at least 1 infusion of BG00002 with at least 1 post-baseline assessment of BG00002 serum concentration; n = the number of participants with an assessment at given timepoint. At Weeks 8, 12, and 16, one participant had values less than the lower limit of quantitation (\<LLQ) and was not counted in the n for that timepoint.

The concentration of BG00002 in serum was determined using an Enzyme Linked Immunosorbent Assay (ELISA).

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Concentration of Natalizumab in Serum Week 0: pre-dose; n=12	NA µg/mL Standard Deviation NA All values were below the limit of quantification.	—
Part A: Concentration of Natalizumab in Serum Week 0: post-dose; n=12	119.4550 µg/mL Standard Deviation 18.86145	—
Part A: Concentration of Natalizumab in Serum Week 0: 4 hours post-dose; n=12	111.8159 µg/mL Standard Deviation 18.35129	—
Part A: Concentration of Natalizumab in Serum Week 0: 24 hours post-dose; n=12	100.5707 µg/mL Standard Deviation 26.17036	—
Part A: Concentration of Natalizumab in Serum Week 0: 48 hours post-dose; n=12	92.5144 µg/mL Standard Deviation 18.26611	—
Part A: Concentration of Natalizumab in Serum Week 0: 96 hours post-dose; n=12	73.2038 µg/mL Standard Deviation 17.02067	—
Part A: Concentration of Natalizumab in Serum 7 days post-dose; n=12	62.3874 µg/mL Standard Deviation 16.49046	—
Part A: Concentration of Natalizumab in Serum 14 days post-dose; n=12	41.2363 µg/mL Standard Deviation 12.02968	—
Part A: Concentration of Natalizumab in Serum 21 days post-dose; n=12	30.9994 µg/mL Standard Deviation 11.45474	—
Part A: Concentration of Natalizumab in Serum Week 4: pre-dose; n=12	22.5702 µg/mL Standard Deviation 9.55131	—
Part A: Concentration of Natalizumab in Serum Week 8: pre-dose; n=11	24.7048 µg/mL Standard Deviation 15.50352	—
Part A: Concentration of Natalizumab in Serum Week 12: pre-dose; n=10	27.9105 µg/mL Standard Deviation 16.06085	—
Part A: Concentration of Natalizumab in Serum Week 16: pre-dose; n=10	32.9645 µg/mL Standard Deviation 16.41578	—
Part A: Concentration of Natalizumab in Serum Week 20: pre-dose; n=10	36.2724 µg/mL Standard Deviation 14.51395	—
Part A: Concentration of Natalizumab in Serum Week 20: post-dose; n=10	145.5353 µg/mL Standard Deviation 38.26877	—
Part A: Concentration of Natalizumab in Serum Week 20: 4 hours post-dose; n=10	137.6666 µg/mL Standard Deviation 30.47429	—
Part A: Concentration of Natalizumab in Serum Week 20: 24 hours post-dose; n=10	130.8829 µg/mL Standard Deviation 30.17375	—
Part A: Concentration of Natalizumab in Serum Week 20: 48 hours post-dose; n=10	120.0772 µg/mL Standard Deviation 28.68860	—
Part A: Concentration of Natalizumab in Serum Week 20: 96 hours post-dose; n=10	103.3549 µg/mL Standard Deviation 26.94133	—
Part A: Concentration of Natalizumab in Serum Week 20: 7 days post-dose; n=10	86.2563 µg/mL Standard Deviation 24.70785	—
Part A: Concentration of Natalizumab in Serum Week 20: 14 days post-dose; n=10	65.7307 µg/mL Standard Deviation 24.60531	—
Part A: Concentration of Natalizumab in Serum Week 20: 21 days post-dose; n=10	52.4002 µg/mL Standard Deviation 21.41919	—
Part A: Concentration of Natalizumab in Serum Week 20: 28 days post-dose; n=10	35.8368 µg/mL Standard Deviation 16.33283	—

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 12, Week 24

Population: Randomized participants who received at least 1 infusion of BG00002 and had at least 1 post-baseline assessment of BG00002 serum concentration; n = the number of these participants with an assessment at given timepoint. Participants with values \<LLQ were not counted in the n for that timepoint.

The concentration of BG00002 in serum was determined using an Enzyme Linked Immunosorbent Assay (ELISA).

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Concentration of Natalizumab in Serum Baseline; n=47	NA µg/mL Standard Deviation NA All participants had values \< LLQ.	—
Part B: Concentration of Natalizumab in Serum Week 12; n=45	32.6475 µg/mL Standard Deviation 14.68246	—
Part B: Concentration of Natalizumab in Serum Week 24; n=45	44.4830 µg/mL Standard Deviation 22.53573	—

SECONDARY outcome

Timeframe: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose

Observed maximum concentration (Cmax) was calculated using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Cmax Dose 1/Week 0; n=12	119.58 µg/mL Interval 89.4 to 166.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Cmax Dose 6/Week 20; n=10	144.36 µg/mL Interval 92.6 to 221.0	—

SECONDARY outcome

Timeframe: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose

Area under the curve to the last measurable concentration (AUC\[0-last\]); and area under the curve extrapolated to infinity (0-AUC∞) were calculated using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: AUC(0-last) and (0-AUC∞) AUC(0-last), Dose 1/Week 0; n=12	31574.6 µg*h/mL Interval 24462.0 to 49818.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: AUC(0-last) and (0-AUC∞) AUC(0-last), Dose 6/Week 20; n=10	46094.8 µg*h/mL Interval 30407.0 to 71319.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: AUC(0-last) and (0-AUC∞) AUC(0-∞), Dose 1/Week 0; n=12	43172.6 µg*h/mL Interval 25631.0 to 68072.0	—

SECONDARY outcome

Timeframe: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose

Time to maximum concentration (Tmax) and half-life (T1/2) were calculated using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2 Tmax, Dose 1/Week 0; n=12	1.49 hours Interval 1.0 to 22.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2 Tmax, Dose 6/Week 20; n=10	2.27 hours Interval 1.0 to 6.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2 T1/2, Dose 1/Week 0; n=12	344.9 hours Interval 158.0 to 697.0	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2 T1/2, Dose 6/Week 20; n=10	381.2 hours Interval 181.0 to 533.0	—

SECONDARY outcome

Timeframe: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose

Volume of distribution (Vd) was calculated using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Vd Dose 1/Week 0; n=12	3.422 L Interval 2.3 to 5.05	—
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Vd Dose 6/Week 20; n=10	3.561 L Interval 2.19 to 6.05	—

SECONDARY outcome

Timeframe: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose

Population: Randomized participants who received at least 1 infusion of BG00002 and had at least 1 post-baseline assessment of BG00002 serum concentration.

Systemic clearance (CL) was calculated using non-compartmental methods.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: CL	6.9497 mL/h Interval 4.41 to 11.7	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Participants with one or more post-baseline screening antibody result.

Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Status of Serum Antibodies to Natalizumab Negative at all post-dose results	47 participants	45 participants
Part B: Status of Serum Antibodies to Natalizumab Positive at any time	0 participants	2 participants
Part B: Status of Serum Antibodies to Natalizumab Positive at final evaluation	0 participants	1 participants
Part B: Status of Serum Antibodies to Natalizumab Persistently positive	0 participants	1 participants

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part B: Number of Participants With Adverse Events (AEs) Participants with an adverse event (AE)	41 participants	34 participants
Part B: Number of Participants With Adverse Events (AEs) Participants with a moderate or severe AE	30 participants	14 participants
Part B: Number of Participants With Adverse Events (AEs) Participants with a severe AE	5 participants	0 participants
Part B: Number of Participants With Adverse Events (AEs) Participants with an AE related to study drug	7 participants	7 participants
Part B: Number of Participants With Adverse Events (AEs) Participants with a serious event (SAE)	11 participants	7 participants
Part B: Number of Participants With Adverse Events (AEs) Participants with an SAE related to study drug	1 participants	1 participants
Part B: Number of Participants With Adverse Events (AEs) Participants discontinuing treatment due to an AE	1 participants	0 participants
Part B: Number of Participants With Adverse Events (AEs) Participants withdrawing from study due to an AE	1 participants	0 participants

SECONDARY outcome

Timeframe: Pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose; Weeks 8, 12, and 16: pre-dose; Week 20: pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose

Population: Participants in Part A who received a dose of BG00002 and had at least 1 post-baseline assessment of α4-integrin saturation; n=participants with an assessment at timepoint.

Pharmacodynamic activity was assessed by measuring the degree of saturation by BG00002 of the very late antigen-4 (VLA-4, also known as α4β1 integrin) receptor on peripheral blood mononuclear cell populations. This was accomplished by staining cells with phycoerythrin-conjugated anti-human immunoglobulin G4 (IgG4) antibody (hIgG4-PE) to label the cell-bound BG00002, followed by flow cytometric detection and quantification.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) 4 hours post-dose (n=12)	88.371 percent saturation Standard Deviation 4.6811	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) 7 days post-dose (n=12)	85.491 percent saturation Standard Deviation 7.1019	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: pre-dose (n=10)	75.314 percent saturation Standard Deviation 7.1022	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Pre-dose (n=12)	6.282 percent saturation Standard Deviation 1.6450	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) 14 days post-dose (n=12)	77.929 percent saturation Standard Deviation 6.8396	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) 21 days post-dose (n=12)	71.362 percent saturation Standard Deviation 6.8992	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) 28 days post-dose (n=12)	69.742 percent saturation Standard Deviation 7.3283	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 8: pre-dose (n=11)	64.057 percent saturation Standard Deviation 20.2412	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 12: pre-dose (n=11)	60.615 percent saturation Standard Deviation 22.0351	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 16: pre-dose (n=10)	75.485 percent saturation Standard Deviation 4.4088	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: 4 hours post-dose (n=10)	88.859 percent saturation Standard Deviation 5.0230	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: 7 days post-dose (n=10)	83.575 percent saturation Standard Deviation 5.9416	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: 14 days post-dose (n=10)	80.376 percent saturation Standard Deviation 5.4459	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: 21 days post-dose (n=10)	80.842 percent saturation Standard Deviation 5.5828	—
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC) Week 20: 28 days post-dose (n=10)	70.897 percent saturation Standard Deviation 4.5757	—

SECONDARY outcome

Timeframe: Baseline [Week 0]); 28 days post-dose; Weeks 12, 24, and 32 (follow-up)

Population: Participants in Part A who received a dose of BG00002 and had at least 1 post-baseline assessment of lymphocytes; n=participants with assessment at timepoint.

Outcome measures

Outcome measures
Measure	Open Label Natalizumab n=12 Participants 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Part A: Summary of Lymphocyte Counts Over Time Screening; n=12	1708.3 cells/microliter Standard Deviation 556.71	—
Part A: Summary of Lymphocyte Counts Over Time Pre-dose; n=12	1775.0 cells/microliter Standard Deviation 534.49	—
Part A: Summary of Lymphocyte Counts Over Time 28 days Post-dose; n=12	3016.7 cells/microliter Standard Deviation 845.13	—
Part A: Summary of Lymphocyte Counts Over Time Week 12; n=11	3018.2 cells/microliter Standard Deviation 1112.49	—
Part A: Summary of Lymphocyte Counts Over Time Week 24; n=10	3340.0 cells/microliter Standard Deviation 939.50	—
Part A: Summary of Lymphocyte Counts Over Time Week 32 Follow-up; n=2	1550.0 cells/microliter Standard Deviation 70.71	—

Adverse Events

Open Label Natalizumab

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Double-Blind Placebo

Serious events: 11 serious events

Other events: 32 other events

Deaths: 0 deaths

Double-Blind Natalizumab

Serious events: 7 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open Label Natalizumab n=12 participants at risk 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Placebo n=47 participants at risk IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 participants at risk 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Eye disorders Retinal Detachment	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Nervous system disorders Multiple Sclerosis Relapse	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	21.3% 10/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	8.5% 4/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Infections and infestations Pyelonephritis	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Psychiatric disorders Asperger's Disorder	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Psychiatric disorders Somatoform Disorder	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.

Other adverse events

Additional Information

Biogen Idec Study Medical Director

Biogen Idec

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 noncommercial 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

Measure	Open Label Natalizumab n=12 participants at risk 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks	Double-Blind Placebo n=47 participants at risk IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks	Double-Blind Natalizumab n=47 participants at risk 300 mg IV infusions of natalizumab (BG00002) over 60 minutes every 4 weeks for 20 weeks
Infections and infestations Nasopharyngitis	25.0% 3/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	29.8% 14/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	19.1% 9/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Infections and infestations Cystitis	16.7% 2/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Infections and infestations Pharyngitis	16.7% 2/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	4.3% 2/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	6.4% 3/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Infections and infestations Acute Sinusitis	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Infections and infestations Bacterial Infection	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Psychiatric disorders Depressed Mood	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Psychiatric disorders Insomnia	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	2.1% 1/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	6.4% 3/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Nervous system disorders Headache	25.0% 3/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Nervous system disorders Multiple Sclerosis Relapse	16.7% 2/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	36.2% 17/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	17.0% 8/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Nervous system disorders Central Nervous System Lesion	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Nervous system disorders Somnolence	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Eye disorders Conjunctivitis Allergic	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Eye disorders Eye Discharge	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Respiratory, thoracic and mediastinal disorders Asthma	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Respiratory, thoracic and mediastinal disorders Dysphonia	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Gastrointestinal disorders Gastric Ulcer	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Skin and subcutaneous tissue disorders Eczema	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	6.4% 3/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	4.3% 2/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Skin and subcutaneous tissue disorders Urticaria	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Musculoskeletal and connective tissue disorders Bursitis	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Reproductive system and breast disorders Dysmenorrhoea	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
General disorders Fatigue	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
General disorders Irritability	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
General disorders Pyrexia	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Injury, poisoning and procedural complications Injury	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Injury, poisoning and procedural complications Road Traffic Accident	8.3% 1/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Eye disorders Asthenopia	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	6.4% 3/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/12 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	6.4% 3/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.	0.00% 0/47 • AEs were collected from Baseline (Week 0) through Week 24 (treatment period) + 20 Weeks (or 24 weeks after last infusion). Serious adverse events (SAEs) were collected from the time of informed consent.