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)

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Placebo; Drug: BIIB033; Drug: Avonex

• Study Type: Interventional
• Enrollment (Actual): 419
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • London, Canada, N6A 5A5
    • London Health Sciences Centre
  • Ontario
    • Ottowa, Ontario, Canada
      • Research Site
  • Quebec
    • Gatinueau, Quebec, Canada
      • Research Site
    • Greenfield Park, Quebec, Canada
      • Research Site
    • Levis, Quebec, Canada
      • Research Site
    • Montreal, Quebec, Canada
      • Research Site
• Czech Republic
  • Havirov, Czech Republic, 736 01
    • NEUROSPOL Sro
  • Praha 5, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
  • Hlavní Mesto
    • Praha, Hlavní Mesto, Czech Republic, 128 08
      • Vseobecna fakultni nemocnice v Praze
  • Královéhradecký kraj
    • Hradec Králové, Královéhradecký kraj, Czech Republic, 500 05
      • Fakultni nemocnice Hradec Kralove
  • Vysocina
    • Jihlava, Vysocina, Czech Republic, 586 33
      • Nemocnice Jihlava příspěvková organizace
  • Ústecký kraj
    • Teplice, Ústecký kraj, Czech Republic, 415 29
      • Krajska Zdravotni a.s. Nemocnice Teplice Oz
• France
  • Clermont-Ferrand, France, 63003
    • Hopital Gabriel Montpied
  • Nancy, France, 54000
    • CHRU Nancy
  • Paris, France, 75019
    • Fondation Rothschild
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44805
      • Hôpital Guillaume et René Laënnec
  • Marne
    • Reims, Marne, France, 51092
      • Hopital Maison Blanche
  • Nord
    • Lille, Nord, France, 59000
      • Hôpital Roger Salengro
  • Somme
    • Amiens, Somme, France, 80054
      • Hopital Sud
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Kórház
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem
  • Csongrád
    • Szeged, Csongrád, Hungary, 6725
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
• Italy
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Azienda Ospedaliera Universitaria San Martino
  • Lombardia
    • Milano, Lombardia, Italy, 20127
      • Ospedale San Raffaele S.r.l.
    • Montichiari, Lombardia, Italy, 25018
      • Azienda Ospedaliera Spedali Civili di Brescia - Presidio Ospedaliero di Montichiari
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Fondazione Istituto San Raffaele G. Giglio di Cefalù
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Azienda Ospedaliero Universitaria Policlinico-Vittorio Emanuele
  • Varese
    • Gallarate, Varese, Italy, 21013
      • Azienda Ospedaliera S. Antonio Abate di Gallarate
• Netherlands
  • Sittard-Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 CE
      • Erasmus MC
• Poland
  • Gdansk, Poland, 80-803
    • Pomorskie Centrum Traumatologii im. M. Kopernika w Gdansku
  • Grudziądz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego
  • Katowice, Poland, 40-595
    • M.A.- Lek A.M.Maciejowscy Spolka Cywilna
  • Katowice, Poland, 40-749
    • Gabriela Klodowska-Duda Neuro-Care NZOZ Site Management Organization
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM Osrodek Badan Klinicznych Dr n. med. Hanka Hertmanowska
  • Poznan, Poland, 61-853
    • Niepubliczny Zaklad Opieki Zdrowotnej NEURO-KARD Ilkowski i Partnerzy Spolka Partnerska Lekarzy
  • Rybnik, Poland, 44-200
    • SPZOZ Wojewodzki Szpital Specjalistyczny w Rybniku
  • Szczecin, Poland, 70-215
    • Euromedis Sp. z o.o.
  • Lódzkie
    • Lódz, Lódzkie, Poland, 93-121
      • Centrum Neurologii K. Selmaj
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 00-901
      • Wojskowy Instytut Medyczny
  • Slaskie
    • Katowice, Slaskie, Poland, 40-650
      • Novo-Med Zielinski i wsp. Sp.J.
• Russian Federation
  • Kaluga, Russian Federation, 248007
    • Kaluga Regional Hospital
  • Kazan, Russian Federation, 420021
    • Republican Clinical Hospital For Rehabilitation Treatment
  • Krasnoyarsk, Russian Federation, 660049
    • Krasnoyarsk State Medical Academy
  • Perm, Russian Federation, 614990
    • Perm State Medical Academy
  • Saint-Petersburg, Russian Federation, 197110
    • City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31
  • Volgograd, Russian Federation, 400001
    • Regional Clinical Hospital #3
• Serbia
  • Belgrade, Serbia, 11000
    • Military Medical Academy
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Uzice, Serbia, 31000
    • General Hospital Uzice
• Spain
  • Malaga, Spain, 29010
    • Hospital General Carlos Haya
  • Sevilla, Spain, 41071
    • Hospital Universitario Virgen Macarena
  • Barcelona
    • l Hospitalet de Llobregat, Barcelona, Spain, 8907
      • Hospital Universitari de Bellvitge
  • Cataluña
    • Barcelona, Cataluña, Spain, 8035
      • Hospital Universitario Vall d'Hebron
  • Córdoba
    • Cordoba, Córdoba, Spain, 14008
      • Hospital Universitario Reina Sofia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
  • Madrid, Communidad Delaware
    • Madrid, Madrid, Communidad Delaware, Spain, 28040
      • Hospital Clinico San Carlos
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto Osakidetza
• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Queen's Medical Centre
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • North Central Neurology Assoc PC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Associates
  • California
    • Raleigh, California, United States, 27607-6000
      • Raleigh Neurology Associates PA
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Latham, New York, United States, 12110
      • Multiple Sclerosis Center of North Eastern New York
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OMRF Multiple Sclerosis Center of Excellence
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: BIIB033; Other Names: anti-LINGO-1 mAb; Drug: Avonex; Other Names: interferon beta-1a
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.	Drug: BIIB033; Other Names: anti-LINGO-1 mAb; Drug: Avonex; Other Names: interferon beta-1a
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.	Drug: BIIB033; Other Names: anti-LINGO-1 mAb; Drug: Avonex; Other Names: interferon beta-1a
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.	Drug: BIIB033; Other Names: anti-LINGO-1 mAb; Drug: Avonex; Other Names: interferon beta-1a
PLACEBO_COMPARATOR: Placebo; Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Other: Placebo; Drug: Avonex; Other Names: interferon beta-1a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint	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.	72 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: May 28, 2013
• First Posted (ESTIMATE): May 29, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2017
• Last Update Submitted That Met QC Criteria: March 23, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Interferon-beta
• Other Study ID Numbers: 215MS201; 2011-006262-40 (EUDRACT_NUMBER)