Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)

NCT03222973 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 215MS2022017-001224-22
• Study Type: interventional
• Target: 263
• Locations: 15 countries
• Sites: 159

Brief Summary

The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in participants with MS. The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on additional measures of disability improvement. The secondary objective of Part 2 is to investigate long-term efficacy (disability improvement) and additional safety measures of BIIB033 as an add-on therapy in participants with MS.

Conditions

Multiple Sclerosis

Keywords

Remyelination; Re-myelination; DMT; LINGO-1; Anti-LINGO-1; Opicinumab

Outcome Measures

Primary Outcomes (2)

• Part 1: Overall Response Score

  Overall Response Score is a multicomponent score based on 4 components: Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the nondominant hand (9HPT-ND). Overall Score was sum of 4 components at each visit and ranges from +4 (improvement) to -4 (worsening). At each visit, each component is given a score relative to baseline (BL): -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement. For T25FW and 9HPT improvement is ≥15% decrease in time from BL and worsening is ≥15% increase in time from BL. For EDSS, improvement is: ≥1.0-point decrease in EDSS from a BL score of ≤6.0, and worsening is defined as a ≥1-point increase from a BL score of ≤5.5 or a ≥0.5-point increase from a BL score equal to 6.0. Positive Overall Response Score indicated that there was improvement in more components than there was worsening.

  Part 1: Baseline to Week 72

• Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.

  Part 2: Baseline to Week 169

Secondary Outcomes (16)

• Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND

  Part 1: Baseline to Week 72

• Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3)

  Part 1: Baseline to Week 72

• Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and Without Confirmed Worsening in Any of the 4 Assessments During the 72 Weeks of the Study

  Part 1: Baseline to Week 72

• Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT)

  Part 1: Baseline to Week 72

• Part 1: Percentage of Participants With 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% Thresholds for T25FW and 9HPT)

  Part 1: Baseline to Week 72

Study Arms (2)

BIIB033 (opicinumab) 750 mg

EXPERIMENTAL

Participants with relapsing multiple sclerosis (RMS) will receive BIIB033 750 milligram (mg) intravenously (IV) as an add-on therapy to a background disease-modifying therapy (DMT) once every 4 weeks over 72 weeks in Part 1 and once every 4 weeks over 96 weeks in Part 2.

Drug: BIIB033 (opicinumab)

Placebo

PLACEBO COMPARATOR

Participants with RMS will receive placebo IV as an add-on therapy to a background DMT once every 4 weeks over 72 weeks in Part 1 and BIIB033 once every 4 weeks over 96 weeks in Part 2. The placebo looks like BIIB033 but does not contain the active ingredient that is thought to have an effect on MS disease. The placebo used in this study is sterile normal saline (water with a small amount of sodium chloride \[salt\]).

Drug: Placebo

Interventions

BIIB033 (opicinumab) DRUG

Administered as specified in the treatment arm

BIIB033 (opicinumab) 750 mg

Placebo DRUG

Administered as specified in the treatment arm

Placebo

Eligibility Criteria

• Age: 18 Years - 58 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald's criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years.
• Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI.
• Subjects must be on a stable dose of a protocol-specified anti-inflammatory disease-modifying therapy (DMT) (IFNβ \[Avonex, Plegridy, Betaferon/Betaseron, or Rebif\], dimethyl fumarate (DMF) \[Tecfidera\], or natalizumab \[Tysabri\]) for at least 24 weeks prior to enrollment.
• In addition, subjects must have met protocol-defined MRI characteristics using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline.
• Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.

You may not qualify if:

• Primary progressive MS
• An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening.
• Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), cell-depleting monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline.
• Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline.
• Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline.
• Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed.
• History of human immunodeficiency virus or other immunodeficient conditions.
• History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.
• Subjects who did not complete study treatment in Part 1/Week 72 Visit
• Subjects who have a duration \>12 weeks between their Part 1/Week 72 Visit and Part 2/Day 1.
• Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to Gd, renal impairment, or claustrophobia that cannot be medically managed.
• History of human immunodeficiency virus or other immunodeficient conditions not related to DMT treatment.
• History of malignancy unless enrollment is approved by the Sponsor; subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

Sponsors & Collaborators

• Biogen: lead

Study Sites (159)

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Cullman, Alabama, 35058, United States

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Gilbert, Arizona, 85234, United States

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Berkeley, California, 94705, United States

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Long Beach, California, 90806, United States

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Newport Beach, California, 92663, United States

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Orange, California, 92868, United States

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Centennial, Colorado, 80112, United States

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Fort Collins, Colorado, 80528, United States

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Stamford, Connecticut, 06905, United States

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Washington D.C., District of Columbia, 20007, United States

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Sunrise, Florida, 33351, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30309, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Overland Park, Kansas, 66212, United States

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Lexington, Kentucky, 40513, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Lexington, Massachusetts, 01805, United States

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Wellesley, Massachusetts, 02481, United States

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Farmington Hills, Michigan, 48334, United States

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Minneapolis, Minnesota, 55422, United States

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St Louis, Missouri, 63110, United States

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St Louis, Missouri, 63131, United States

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Las Vegas, Nevada, 89106, United States

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Freehold, New Jersey, 07728, United States

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Teaneck, New Jersey, 07666, United States

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Latham, New York, 12110, United States

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New York, New York, 10021, United States

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Patchogue, New York, 11772, United States

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Rochester, New York, 14642, United States

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Stony Brook, New York, 11794, United States

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Durham, North Carolina, 27710, United States

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Raleigh, North Carolina, 27607, United States

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Columbus, Ohio, 43214, United States

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Dayton, Ohio, 45417, United States

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Oklahoma City, Oklahoma, 73104, United States

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Portland, Oregon, 97225, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Willow Grove, Pennsylvania, 19090, United States

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Knoxville, Tennessee, 37922, United States

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Memphis, Tennessee, 38018, United States

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Dallas, Texas, 75390-8806, United States

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Houston, Texas, 77030, United States

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Round Rock, Texas, 78681, United States

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Orem, Utah, 84058, United States

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Salt Lake City, Utah, 84103, United States

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Seattle, Washington, 98122, United States

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Seattle, Washington, 98133, United States

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Box Hill, Victoria, 3128, Australia

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Clayton, Victoria, 3168, Australia

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Heidelberg, Victoria, 3084, Australia

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Melbourne, Victoria, 3004, Australia

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Parkville, Victoria, 3050, Australia

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New Lambton Heights, NS 2305, Australia

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Westmead, 2145, Australia

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Bruges, 8000, Belgium

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Brussels, 1090, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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La Louvière, 7100, Belgium

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Leuven, 3000, Belgium

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Roeselare, 8800, Belgium

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Edmonton, Alberta, T6G 1Z1, Canada

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Vancouver, British Columbia, V6T 1Z3, Canada

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Victoria, British Columbia, V8R 1J8, Canada

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Ottawa, Ontario, K1H8L6, Canada

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Toronto, Ontario, M5B1W8, Canada

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Gatineau, Quebec, J8Y 1W2, Canada

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Longueuil, Quebec, J4V2J2, Canada

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Montreal, Quebec, H3A 2B4, Canada

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Brno, 65691, Czechia

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Brno, 66491, Czechia

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Hradec Králové, 50005, Czechia

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Jihlava, 58601, Czechia

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Pardubice, 53203, Czechia

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Prague, 12808, Czechia

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Strasbourg, Bas Rhin, 67098, France

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Nîmes, Gard, 30029, France

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Bordeaux, Gironde, 33076, France

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Toulouse, Haute Garonne, 31059, France

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Montpellier, Herault, 34295, France

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Nantes, Loire Atlantique, 44093, France

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Lille, Nord, 59000, France

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Clermont-Ferrand, Puy De Dome, 63003, France

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Bron, Rhone, 69500, France

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Amiens, Somme, 80054, France

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Paris, 75013, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Ulm, Baden-Wurttemberg, 89081, Germany

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Munich, Bavaria, 81675, Germany

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Bochum, North Rhine-Westphalia, 44791, Germany

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Düsseldorf, North Rhine-Westphalia, 40225, Germany

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Trier, Rhineland-Palatinate, 54292, Germany

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Dresden, Saxony, 1307, Germany

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Berlin, 10117, Germany

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Münster, 48149, Germany

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Budapest, 1135, Hungary

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Budapest, 1145, Hungary

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Budapest, H-1204, Hungary

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Esztergom, 2500, Hungary

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Kistarcsa, 2143, Hungary

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Pécs, 7623, Hungary

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Ramat Gan, 5262000, Israel

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Montichiari, Brescia, 25018, Italy

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Pozzilli, Isernia, 86077, Italy

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Cefalù, Palermo, 90015, Italy

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Genova, 16132, Italy

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Messina, 98124, Italy

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Milan, 20132, Italy

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Milan, 20133, Italy

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Napoli, 80055, Italy

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Napoli, 80131, Italy

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Napoli, 80138, Italy

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Pisa, 56126, Italy

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Roma, 185, Italy

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Verona, 37134, Italy

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Geleen, 6162 AP, Netherlands

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Bydgoszcz, 85-795, Poland

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Gdansk, 80-803, Poland

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Katowice, 40-571, Poland

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Katowice, 40-650, Poland

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Krakow, 31-637, Poland

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Lodz, 90-324, Poland

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Lublin, 20-954, Poland

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Szczecin, 70-111, Poland

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Warsaw, 04-749, Poland

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Zabrze, 41-800, Poland

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Salt, Girona, 17190, Spain

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Majadahonda, Madrid, 28222, Spain

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Barakaldo, Vizcaya, 48903, Spain

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Barcelona, 08907, Spain

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Barcelona, 8035, Spain

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Barcelona, 8036, Spain

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Córdoba, 14004, Spain

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Madrid, 28006, Spain

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Seville, 41009, Spain

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Aarau, 5001, Switzerland

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Basel, 4031, Switzerland

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Bern, 3010, Switzerland

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Lugano, 6903, Switzerland

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Zurich, 8091, Switzerland

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Exeter, Devon, EX2 5DW, United Kingdom

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Plymouth, Devon, PL6 8DH, United Kingdom

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London, Greater London, SE5 9RS, United Kingdom

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London, Greater London, W6 8RF, United Kingdom

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Salford, Greater Manchester, M6 8HD, United Kingdom

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Liverpool, Merseyside, L9 7LJ, United Kingdom

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Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

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Oxford, Oxfordshire, OX3 9DU, United Kingdom

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Glasgow, Strathclyde, G51 4TF, United Kingdom

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Newcastle upon Tyne, Tyne & Wear, NE1 4LP, United Kingdom

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Leeds, West Yorkshire, LS1 3EX, United Kingdom

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Brighton, BN2 5BE, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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Swansea, SA6 6NL, United Kingdom

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Related Publications (3)

• Calabresi PA, Giovannoni G, Hartung HP, Naismith RT, Fox RJ, Sormani MP, Arnold DL, Kappos L, Valis M, Newsome SD, Belkin MI, Bartholome E, Riester K, Javor A, Lyons J, Bradley DP, Fisher E, Tagge I, Naylor ML, Belachew S, Deykin A, Franchimont N, Zhu B, Cheng W. Safety and efficacy of opicinumab in participants with relapsing multiple sclerosis (AFFINITY Part 1): A randomized, controlled, phase 2 trial. Mult Scler. 2026 Jan;32(1):107-120. doi: 10.1177/13524585251396433. Epub 2025 Dec 26.

  PMID: 41454463 DERIVED

• Elliott C, Rudko DA, Arnold DL, Fetco D, Elkady AM, Araujo D, Zhu B, Gafson A, Tian Z, Belachew S, Bradley DP, Fisher E. Lesion-level correspondence and longitudinal properties of paramagnetic rim and slowly expanding lesions in multiple sclerosis. Mult Scler. 2023 May;29(6):680-690. doi: 10.1177/13524585231162262. Epub 2023 Apr 10.

  PMID: 37036134 DERIVED

• Hanf KJM, Arndt JW, Liu Y, Gong BJ, Rushe M, Sopko R, Massol R, Smith B, Gao Y, Dalkilic-Liddle I, Lee X, Mojta S, Shao Z, Mi S, Pepinsky RB. Functional activity of anti-LINGO-1 antibody opicinumab requires target engagement at a secondary binding site. MAbs. 2020 Jan-Dec;12(1):1713648. doi: 10.1080/19420862.2020.1713648.

  PMID: 31928294 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

opicinumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The top-line results from the Part 1 did not meet the pre-specified primary endpoint nor the key secondary endpoints. The decision to discontinue study 215MS202 Part 2 was not based on safety concerns.

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 19, 2017
• Study Start: November 15, 2017
• Primary Completion: February 12, 2021
• Study Completion: February 12, 2021
• Last Updated: April 28, 2022
• Results First Posted: April 28, 2022

Record last verified: 2022-03

Locations

FR (11); IT (13); PL (10); GB (14); AU (7); ES (9); CH (5); CZ (6); BE (7); US (51); IL (1); CA (8); HU (6); NL (1); DE (10)