A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With Optional Open-Label Extension in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies
Overview
- Phase
- Phase 2
- Intervention
- BIIB033 (opicinumab)
- Conditions
- Multiple Sclerosis
- Sponsor
- Biogen
- Enrollment
- 263
- Locations
- 1
- Primary Endpoint
- Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Key Inclusion Criteria: Part 2
- •Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.
Exclusion Criteria
- •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.
- •Key Exclusion Criteria: Part 2
- •Subjects who did not complete study treatment in Part 1/Week 72 Visit
Arms & Interventions
BIIB033 (opicinumab) 750 mg
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.
Intervention: BIIB033 (opicinumab)
Placebo
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 \[salt\]).
Intervention: Placebo
Outcomes
Primary Outcomes
Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Part 2: Baseline to Week 169
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 1: Overall Response Score
Time Frame: Part 1: Baseline to Week 72
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.
Secondary Outcomes
- Part 2: Overall Response Score(Part 2: Baseline to Week 96)
- Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND(Part 2: Baseline to Week 108)
- Part 2: Percentage of Participants With 24-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 96 Weeks of the Study(Part 2: Baseline to Week 96)
- 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 2: Percentage of Participants With 24-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 2: Baseline to Week 108)
- Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values(Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96)
- Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit(Part 2: Baseline to Week 96)
- 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, 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)
- Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and SDMT(Part 2: Baseline to Week 108)
- Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values(Part 2: Baseline to Week 96)
- Part 2: Percentage of Participants With 24-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or PASAT-3(Part 2: Baseline to Week 108)
- Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values(Part 2: Baseline to Week 96)
- Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values(Part 2: Baseline to Week 96)