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)

• ClinicalTrials.gov Identifier: NCT01864148
• Recruitment Status: Completed
• First Posted: May 29, 2013
• Results First Posted: May 3, 2017
• Last Update Posted: May 3, 2017
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: May 24, 2013
• First Posted Date: May 29, 2013
• Results First Submitted Date: March 23, 2017
• Results First Posted Date: May 3, 2017
• Last Update Posted Date: May 3, 2017
• Study Start Date: August 2013
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2017)

Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint [ Time Frame: 72 weeks ]

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.

• Original Primary Outcome Measures (submitted: May 28, 2013): Percentage of subjects experiencing confirmed improvement of neuro-physical and/or cognitive function and/or disability. [ Time Frame: Over 72 weeks ]

Current Secondary Outcome Measures (submitted: March 23, 2017)

• Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint [ Time Frame: 72 weeks ]
  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.
• Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs [ Time Frame: Up to 84 weeks ]
  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.
• Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84 [ Time Frame: Up to 84 weeks ]

Original Secondary Outcome Measures (submitted: May 28, 2013)

• Percentage of subjects experiencing confirmed worsening of neuro-physical and/or cognitive function and/or disability [ Time Frame: Over 72 weeks ]
• Number of participants with Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 84 weeks ]
• BIIB033 population Pharmacokinetics assessment [ Time Frame: Up to 84 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Participants With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BIIB033 in Subjects With Relapsing Forms of Multiple Sclerosis When Used Concurrently With Avonex

Brief Summary

The primary objective of the study is to evaluate the efficacy of BIIB033 in participants with active relapsing multiple sclerosis (MS) when used concurrently with Avonex.

Secondary objectives of this study in this study population are to assess the safety, tolerability, and population pharmacokinetics of BIIB033 when used concurrently with Avonex.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Drug: BIIB033
  Other Name: anti-LINGO-1 mAb
• Other: Placebo
• Drug: Avonex
  Other Name: interferon beta-1a

Study Arms

• Experimental: BIIB033, 3 mg/kg

  BIIB033 3 mg/kg once every 4 weeks intravenous (IV) infusion up to Week 72.

  Avonex once-weekly intramuscular (IM) injection up to Week 84.

  Interventions:

  • Drug: BIIB033
  • Drug: Avonex
• Experimental: BIIB033, 10 mg/kg

  BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72.

  Avonex once-weekly IM injection up to Week 84.

  Interventions:

  • Drug: BIIB033
  • Drug: Avonex
• Experimental: BIIB033, 30 mg/kg

  BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72.

  Avonex once-weekly IM injection up to Week 84.

  Interventions:

  • Drug: BIIB033
  • Drug: Avonex
• Experimental: BIIB033, 100 mg/kg

  BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72.

  Avonex once-weekly IM injection up to Week 84.

  Interventions:

  • Drug: BIIB033
  • Drug: Avonex
• Placebo Comparator: Placebo

  Placebo once every 4 weeks IV infusion up to Week 72.

  Avonex once-weekly IM injection up to Week 84.

  Interventions:

  • Other: Placebo
  • Drug: Avonex

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 5, 2014): 419
• Original Estimated Enrollment (submitted: May 28, 2013): 396
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Diagnosis of relapsing remitting MS (RRMS) or onset of secondary progressive MS (SPMS)
• RRMS and SPMS subjects must have evidence of ongoing disease activity within 12 months of enrollment.
• All male and female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment

Key Exclusion Criteria:

• A MS relapse that has occurred within the 90 days prior to Day 1/Baseline and/or the subject has not stabilized from a previous relapse prior to Screening
• Previous history of clinically significant disease.
• Plans to undergo elective major procedures/surgeries at any time during the study.
• Treatment with any investigational MS drugs within 3 weeks or 5 times the half life (whichever is longer) prior to Day 1/Baseline
• RRMS subjects with any history of inadequate response to any approved interferon β preparation
• History of human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B virus
• History or evidence of drug or alcohol abuse within 2 years prior to randomization

Note: Other protocol defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 58 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czech Republic, France, Hungary, Italy, Netherlands, Poland, Russian Federation, Serbia, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT01864148
• Other Study ID Numbers: 215MS201; 2011-006262-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: Same as current
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: March 2017