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

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2017-001224-22-BE
• Date of registration: 08/09/2017
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: Efficacy and Safety of BIIB033 as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)
• Scientific title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study 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 - Efficacy and Safety of BIIB033 as an Add-on Therapy to DMTs in RMS
• Date of first enrolment: 02/02/2018
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001224-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: 215MS202 Clinical Trial Team
• Affiliation: Biogen Idec Research Limited

• Name: 215MS202 Clinical Trial Team
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
Key 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 protocolspecified anti-inflammatory disease-modifying therapies
(DMT) (IFNß [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 consistent with the presence of demyelination and relatively well-preserved tissue integrity. For enrollment, subjects must meet the following MRI criteria on the Screening/Baseline brain MRI: magnetization transfer ratio (MTR) in T2 lesions =-0.17 normalized MTR unit and diffusion tensor imaging (DTI) – radial diffusivity in T2 lesions =0.98 × 10-3 mm2/s
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Key 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), celldepleting
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple Sclerosis
MedDRA version: 20.0 Level: PT Classification code 10067063 Term: Progressive relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Opicinumab
Product Code: BIIB033
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Opicinumab
Other descriptive name: BIIB033 (ANTI-LINGO)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: Evaluate effects of BIIB033 versus placebo on additional measures of disability improvement
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
- Proportion of subjects 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)
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and without
confirmed worsening in any of 4 assessments during 72 weeks of study
- Proportion of subjects 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)
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% thresholds
for T25FW and 9HPT)

Timepoint(s) of evaluation of this end point: Assessed every 12 weeks from Baseline to Week 72

Main Objective: To evaluate the efficacy and safety of BIIB033 used as add-on therapy to DMTs in subjects with relapsing multiple sclerosis (RMS).

Primary end point(s): 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 (9HPTND). It assesses overall changes in disability over time. Overall Score ranges from +4 to -4. At each visit, each
component is given a score relative to baseline: -1 if threshold is met for worsening, 0 if no changes meet threshold
criteria, or +1 if threshold is met for improvement. The thresholds for T25FW and 9HPT are defined by a 15%
change from baseline (=15% decrease from baseline for improvement and =15% increase from baseline for worsening). For EDSS, improvement is defined as a =1.0-point decrease in EDSS from a baseline score of =6.0, and worsening is defined as a =1-point increase from a baseline score of =5.5 or a =0.5-point increase from a baseline score equal to 6.0.

Secondary Outcome(s)

Secondary end point(s): - Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
- 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)
- 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
- 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)
- 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)

Timepoint(s) of evaluation of this end point: Assessed every 12 weeks from Baseline to Week 72

Secondary ID(s)

2017-001224-22-GB

215MS202

Source(s) of Monetary Support

Biogen Idec Research Limited

Ethics review

Status: Approved
Approval date: 02/02/2018
Contact: