Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Participants With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex (SYNERGY)

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ClinicalTrials.gov Identifier: NCT01864148

Recruitment Status : Completed

First Posted : May 29, 2013

Results First Posted : May 3, 2017

Last Update Posted : May 3, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Biogen

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Multiple Sclerosis
Interventions	Drug: BIIB033 Other: Placebo Drug: Avonex
Enrollment	419

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 419 participants were randomized; 1 participant was not dosed.


Arm/Group Title	Placebo	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg
Arm/Group Description	Placebo once every 4 weeks intraven...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...
Arm/Group Description	Placebo once every 4 weeks intravenous (IV) infusion up to Week 72. Avonex once-weekly intramuscular (IM) injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
Period Title: Overall Study
Started	93	45	95	94	92
Randomized and Dosed	93	45	95	93	92
Completed	73	40	84	68	69
Not Completed	20	5	11	26	23
Reason Not Completed
Other	2	1	1	3	1
Death	0	0	0	1	0
Investigator Decision	5	0	0	4	6
Withdrawal by Subject	9	2	6	8	8
Lost to Follow-up	0	0	0	2	1
Adverse Event	4	2	4	7	7
Not Dosed	0	0	0	1	0

Baseline Characteristics

Arm/Group Title		Placebo	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg	Total
Arm/Group Description		Placebo once every 4 weeks IV infus...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...	Total of all reporting groups
Arm/Group Description		Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Total of all reporting groups
Overall Number of Baseline Participants		93	45	95	93	92	418
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	93 participants	45 participants	95 participants	93 participants	92 participants	418 participants
		39.5 (9.29)	36.5 (9.47)	40.5 (9.78)	40.9 (9.70)	39.8 (9.10)	39.8 (9.51)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	93 participants	45 participants	95 participants	93 participants	92 participants	418 participants
	Female	67 72.0%	24 53.3%	59 62.1%	61 65.6%	66 71.7%	277 66.3%
	Male	26 28.0%	21 46.7%	36 37.9%	32 34.4%	26 28.3%	141 33.7%

Outcome Measures

1.Primary Outcome


Title	Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint
Description	Estimated proportion of participants experiencing confirmed improvemen...
Description	Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of <=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments.
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and included in the efficacy analysis (6 participants were excluded due to study site Good Clinical Practice deviation).


Arm/Group Title	Placebo	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg
Arm/Group Description:	Placebo once every 4 weeks IV infus...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...
Arm/Group Description:	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
Overall Number of Participants Analyzed	91	45	94	91	91
Measure Type: Number Unit of Measure: proportion of participants
	0.516	0.511	0.656	0.688	0.412

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9584
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95% 0.46 to 2.07
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0636
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95% 0.97 to 3.31
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 30 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0220
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95% 1.11 to 3.84
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 100 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1771
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% 0.36 to 1.21
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 3 mg/kg, BIIB033, 10 mg/kg, BIIB033, 30 mg/kg, BIIB033, 100 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8931
	Comments	[Not Specified]
	Method	Trend test
	Comments	Trend test p-value is based on a linear contrast in logistic regression.

2.Secondary Outcome


Title	Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint
Description	Estimated proportion of participants experiencing confirmed clinical w...
Description	Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments.
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg
Arm/Group Description:	Placebo once every 4 weeks IV infus...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...
Arm/Group Description:	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
Overall Number of Participants Analyzed	91	45	94	91	91
Measure Type: Number Unit of Measure: proportion of participants
	0.403	0.304	0.509	0.489	0.369

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 3 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3058
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95% 0.28 to 1.49
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 10 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1873
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95% 0.81 to 2.89
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 30 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.2766
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95% 0.76 to 2.65
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 100 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6578
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.45 to 1.65
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, BIIB033, 3 mg/kg, BIIB033, 10 mg/kg, BIIB033, 30 mg/kg, BIIB033, 100 mg/kg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5255
	Comments	[Not Specified]
	Method	Trend test
	Comments	Trend test p-value is based on a linear contrast in logistic regression.

3.Secondary Outcome


Title	Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs
Description	An AE was any untoward medical occurrence that did not necessarily hav...
Description	An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above.
Time Frame	Up to 84 weeks

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study treatment.


Arm/Group Title	Placebo	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg	BIIB033 Total
Arm/Group Description:	Placebo once every 4 weeks IV infus...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...	BIIB033 3, 10, 30, or 100 mg/kg onc...
Arm/Group Description:	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3, 10, 30, or 100 mg/kg once every 4 weeks IV infusion
Overall Number of Participants Analyzed	93	45	95	93	92	325
Measure Type: Number Unit of Measure: participants
Any event	79	39	84	79	73	275
Moderate or severe event	59	26	59	59	58	202
Severe event	7	2	6	6	7	21
BIIB033/placebo-related event	8	8	15	12	16	51
Avonex-related event	51	28	58	54	50	190
Serious event	13	4	11	20	16	51
BIIB033/placebo-related serious event	1	0	0	1	5	6
Avonex-related serious event	1	0	0	2	1	3
Event leading to discontinuation of treatment	4	2	3	7	8	20
Event leading to withdrawal from study	4	2	4	8	7	21

4.Secondary Outcome


Title	Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Up to 84 weeks

Outcome Measure Data

Analysis Population Description

PK Population: participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data point on record.


Arm/Group Title	BIIB033, 3 mg/kg	BIIB033, 10 mg/kg	BIIB033, 30 mg/kg	BIIB033, 100 mg/kg
Arm/Group Description:	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...
Arm/Group Description:	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
Overall Number of Participants Analyzed	45	95	92	92
Mean (Standard Deviation) Unit of Measure: µg/mL
Baseline, predose; n=44, 95, 92, 92	0.00 (0.00)	0.01 (0.13)	7.79 (74.75)	0.42 (4.07)
Baseline, postdose; n=44, 95, 91, 92	66.70 (16.00)	244.76 (77.90)	688.47 (245.73)	2298.20 (712.91)
Week 4, predose; n=45, 93, 91, 88	10.82 (4.11)	46.28 (33.15)	138.54 (92.82)	457.96 (308.09)
Week 4, postdose; n=45, 94, 89, 85	123.96 (315.66)	279.67 (100.01)	784.08 (204.31)	2763.26 (823.42)
Week 8, predose; n=45, 95, 89, 85	23.55 (54.96)	65.48 (52.53)	195.29 (118.24)	603.11 (425.58)
Week 8, postdose; n=44, 94, 88, 79	86.29 (52.74)	294.44 (78.61)	861.60 (274.56)	2751.25 (697.42)
Week 16, predose; n=43, 94, 86, 79	19.96 (9.74)	71.80 (25.13)	231.94 (125.42)	695.11 (438.57)
Week 16, postdose; n=41, 93, 85, 78	85.95 (29.04)	309.38 (83.38)	881.45 (211.32)	2921.09 (1118.88)
Week 24, predose; n=42, 93, 85, 74	36.41 (85.48)	77.88 (33.68)	230.46 (77.40)	699.63 (400.49)
Week 24, postdose; n=42, 92, 82, 76	144.12 (373.36)	318.01 (84.74)	940.29 (231.35)	2870.29 (874.28)
Week 36, predose; n=41, 88, 79, 74	25.33 (18.28)	85.05 (44.67)	238.48 (73.75)	725.22 (344.01)
Week 36, postdose; n=42, 88, 77, 73	94.62 (21.89)	339.17 (88.96)	197.86 (197.96)	3048.66 (989.34)
Week 48, predose; n=39, 85, 74, 70	20.78 (6.26)	80.28 (31.62)	272.88 (167.79)	806.70 (541.78)
Week 48, postdose; n=42, 85, 75, 72	90.07 (23.37)	334.12 (78.43)	955.25 (193.34)	3167.07 (1144.25)
Week 60, predose; n=41, 84, 70, 68	21.29 (12.34)	81.77 (30.24)	243.18 (78.57)	694.12 (200.41)
Week 60, postdose; n=42, 84, 71, 71	93.11 (35.98)	335.10 (93.29)	939.17 (255.64)	3330.70 (1076.88)
Week 72, predose; n=41, 85, 72, 68	19.53 (9.34)	78.94 (29.95)	215.09 (62.98)	819.39 (577.60)
Week 72, postdose; n=38, 84, 69, 68	82.96 (31.84)	313.13 (87.22)	868.39 (231.14)	3145.82 (1233.66)
Week 84; n=40, 81, 69, 69	2.44 (1.25)	12.77 (6.80)	46.16 (31.52)	127.69 (65.46)

Adverse Events

Time Frame	From first dosing of study treatment through end of study (Week 84)
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Placebo	BIIB033 3 mg/kg	BIIB033 10 mg/kg	BIIB033 30 mg/kg	BIIB033 100 mg/kg
Arm/Group Description	Placebo once every 4 weeks IV infus...	BIIB033 3 mg/kg once every 4 weeks ...	BIIB033 10 mg/kg once every 4 weeks...	BIIB033 30 mg/kg once every 4 weeks...	BIIB033 100 mg/kg once every 4 week...
Arm/Group Description	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	BIIB033 3 mg/kg once every 4 weeks IV infusion	BIIB033 10 mg/kg once every 4 weeks IV infusion	BIIB033 30 mg/kg once every 4 weeks IV infusion	BIIB033 100 mg/kg once every 4 weeks IV infusion
All-Cause Mortality
	Placebo	BIIB033 3 mg/kg	BIIB033 10 mg/kg	BIIB033 30 mg/kg	BIIB033 100 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Placebo	BIIB033 3 mg/kg	BIIB033 10 mg/kg	BIIB033 30 mg/kg	BIIB033 100 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	13/93 (13.98%)	4/45 (8.89%)	11/95 (11.58%)	20/93 (21.51%)	16/92 (17.39%)
Blood and lymphatic system disorders
Hypochromic anaemia ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Cardiac disorders
Acute myocardial infarction ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Myocardial infarction ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Myocardial ischaemia ^† 1	0/93 (0.00%)	1/45 (2.22%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Gastrointestinal disorders
Ileus ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Pancreatitis ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Small intestinal obstruction ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Hepatobiliary disorders
Bile duct stone ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Cholecystitis acute ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Drug-induced liver injury ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Immune system disorders
Hypersensitivity ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	4/92 (4.35%)
Infections and infestations
Cystitis ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Urinary tract infection ^† 1	2/93 (2.15%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Injury, poisoning and procedural complications
Fall ^† 1	0/93 (0.00%)	1/45 (2.22%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Femur fracture ^† 1	0/93 (0.00%)	1/45 (2.22%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Intentional overdose ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Road traffic accident ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Investigations
Hepatic enzyme increased ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Musculoskeletal and connective tissue disorders
Osteoarthritis ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Malignant melanoma ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Thyroid adenoma ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Uterine leiomyoma ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Nervous system disorders
Multiple sclerosis ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Multiple sclerosis relapse ^† 1	7/93 (7.53%)	2/45 (4.44%)	6/95 (6.32%)	10/93 (10.75%)	6/92 (6.52%)
Radicular syndrome ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Secondary progressive multiple sclerosis ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Seizure ^† 1	1/93 (1.08%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Trigeminal neuralgia ^† 1	0/93 (0.00%)	1/45 (2.22%)	0/95 (0.00%)	0/93 (0.00%)	0/92 (0.00%)
Psychiatric disorders
Acute psychosis ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Anxiety ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Bipolar disorder ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Bipolar I disorder ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
Suicidal ideation ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Menorrhagia ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	1/93 (1.08%)	0/92 (0.00%)
Metrorrhagia ^† 1	0/93 (0.00%)	0/45 (0.00%)	1/95 (1.05%)	0/93 (0.00%)	0/92 (0.00%)
Uterine polyp ^† 1	0/93 (0.00%)	0/45 (0.00%)	0/95 (0.00%)	0/93 (0.00%)	1/92 (1.09%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	BIIB033 3 mg/kg	BIIB033 10 mg/kg	BIIB033 30 mg/kg	BIIB033 100 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	74/93 (79.57%)	38/45 (84.44%)	79/95 (83.16%)	70/93 (75.27%)	67/92 (72.83%)
Gastrointestinal disorders
Diarrhoea ^† 1	3/93 (3.23%)	5/45 (11.11%)	3/95 (3.16%)	3/93 (3.23%)	3/92 (3.26%)
General disorders
Asthenia ^† 1	8/93 (8.60%)	1/45 (2.22%)	5/95 (5.26%)	6/93 (6.45%)	3/92 (3.26%)
Chills ^† 1	5/93 (5.38%)	4/45 (8.89%)	4/95 (4.21%)	8/93 (8.60%)	4/92 (4.35%)
Fatigue ^† 1	8/93 (8.60%)	6/45 (13.33%)	5/95 (5.26%)	7/93 (7.53%)	7/92 (7.61%)
Influenza like illness ^† 1	37/93 (39.78%)	17/45 (37.78%)	51/95 (53.68%)	34/93 (36.56%)	38/92 (41.30%)
Pyrexia ^† 1	7/93 (7.53%)	9/45 (20.00%)	8/95 (8.42%)	12/93 (12.90%)	11/92 (11.96%)
Infections and infestations
Influenza ^† 1	4/93 (4.30%)	3/45 (6.67%)	6/95 (6.32%)	4/93 (4.30%)	6/92 (6.52%)
Nasopharyngitis ^† 1	16/93 (17.20%)	3/45 (6.67%)	12/95 (12.63%)	8/93 (8.60%)	10/92 (10.87%)
Pharyngitis ^† 1	2/93 (2.15%)	5/45 (11.11%)	4/95 (4.21%)	3/93 (3.23%)	3/92 (3.26%)
Sinusitis ^† 1	5/93 (5.38%)	2/45 (4.44%)	2/95 (2.11%)	0/93 (0.00%)	2/92 (2.17%)
Upper respiratory tract infection ^† 1	13/93 (13.98%)	4/45 (8.89%)	21/95 (22.11%)	11/93 (11.83%)	9/92 (9.78%)
Urinary tract infection ^† 1	12/93 (12.90%)	7/45 (15.56%)	14/95 (14.74%)	9/93 (9.68%)	13/92 (14.13%)
Injury, poisoning and procedural complications
Fall ^† 1	10/93 (10.75%)	0/45 (0.00%)	4/95 (4.21%)	8/93 (8.60%)	5/92 (5.43%)
Investigations
Alanine aminotransferase increased ^† 1	3/93 (3.23%)	2/45 (4.44%)	5/95 (5.26%)	6/93 (6.45%)	7/92 (7.61%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	3/93 (3.23%)	2/45 (4.44%)	4/95 (4.21%)	7/93 (7.53%)	3/92 (3.26%)
Back pain ^† 1	9/93 (9.68%)	3/45 (6.67%)	9/95 (9.47%)	6/93 (6.45%)	6/92 (6.52%)
Muscle spasms ^† 1	3/93 (3.23%)	3/45 (6.67%)	2/95 (2.11%)	2/93 (2.15%)	1/92 (1.09%)
Musculoskeletal pain ^† 1	1/93 (1.08%)	3/45 (6.67%)	1/95 (1.05%)	2/93 (2.15%)	2/92 (2.17%)
Myalgia ^† 1	5/93 (5.38%)	1/45 (2.22%)	5/95 (5.26%)	4/93 (4.30%)	3/92 (3.26%)
Pain in extremity ^† 1	4/93 (4.30%)	5/45 (11.11%)	5/95 (5.26%)	7/93 (7.53%)	1/92 (1.09%)
Nervous system disorders
Headache ^† 1	23/93 (24.73%)	8/45 (17.78%)	19/95 (20.00%)	13/93 (13.98%)	11/92 (11.96%)
Multiple sclerosis relapse ^† 1	30/93 (32.26%)	17/45 (37.78%)	35/95 (36.84%)	36/93 (38.71%)	28/92 (30.43%)
Psychiatric disorders
Anxiety ^† 1	4/93 (4.30%)	0/45 (0.00%)	5/95 (5.26%)	2/93 (2.15%)	3/92 (3.26%)
Depressed mood ^† 1	2/93 (2.15%)	3/45 (6.67%)	1/95 (1.05%)	2/93 (2.15%)	1/92 (1.09%)
Depression ^† 1	6/93 (6.45%)	2/45 (4.44%)	6/95 (6.32%)	7/93 (7.53%)	2/92 (2.17%)
Insomnia ^† 1	1/93 (1.08%)	2/45 (4.44%)	4/95 (4.21%)	6/93 (6.45%)	5/92 (5.43%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

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Name/Title:	Biogen Study Medical Director
Organization:	Biogen
EMail:	clinicaltrials@biogen.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cadavid D, Mellion M, Hupperts R, Edwards KR, Calabresi PA, Drulovic J, Giovannoni G, Hartung HP, Arnold DL, Fisher E, Rudick R, Mi S, Chai Y, Li J, Zhang Y, Cheng W, Xu L, Zhu B, Green SM, Chang I, Deykin A, Sheikh SI; SYNERGY study investigators. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019 Sep;18(9):845-856. doi: 10.1016/S1474-4422(19)30137-1. Epub 2019 Jul 5.

Wilhelm H, Schabet M. The Diagnosis and Treatment of Optic Neuritis. Dtsch Arztebl Int. 2015 Sep 11;112(37):616-25; quiz 626. doi: 10.3238/arztebl.2015.0616.

Layout table for additonal information

Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT01864148
Other Study ID Numbers:	215MS201 2011-006262-40 ( EudraCT Number )
First Submitted:	May 24, 2013
First Posted:	May 29, 2013
Results First Submitted:	March 23, 2017
Results First Posted:	May 3, 2017
Last Update Posted:	May 3, 2017

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