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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03222973




Registration number
NCT03222973
Ethics application status
Date submitted
17/07/2017
Date registered
19/07/2017
Date last updated
28/04/2022

Titles & IDs
Public title
Efficacy and Safety of BIIB033 (Opicinumab) 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 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
Secondary ID [1] 0 0
2017-001224-22
Secondary ID [2] 0 0
215MS202
Universal Trial Number (UTN)
Trial acronym
AFFINITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BIIB033 (opicinumab)
Treatment: Drugs - Placebo

Experimental: 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.

Placebo comparator: 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 \[salt\]).


Treatment: Drugs: BIIB033 (opicinumab)
Administered as specified in the treatment arm

Treatment: Drugs: Placebo
Administered as specified in the treatment arm
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Overall Response Score
Timepoint [1] 0 0
Part 1: Baseline to Week 72
Primary outcome [2] 0 0
Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Part 2: Baseline to Week 169
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Part 1: Baseline to Week 72
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Part 1: Baseline to Week 72
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Part 1: Baseline to Week 72
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Part 1: Baseline to Week 72
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Part 1: Baseline to Week 72
Secondary outcome [6] 0 0
Part 2: Overall Response Score
Timepoint [6] 0 0
Part 2: Baseline to Week 96
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Part 2: Baseline to Week 108
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Part 2: Baseline to Week 108
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Part 2: Baseline to Week 96
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Part 2: Baseline to Week 108
Secondary outcome [11] 0 0
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)
Timepoint [11] 0 0
Part 2: Baseline to Week 108
Secondary outcome [12] 0 0
Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values
Timepoint [12] 0 0
Part 2: Baseline to Week 96
Secondary outcome [13] 0 0
Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values
Timepoint [13] 0 0
Part 2: Baseline to Week 96
Secondary outcome [14] 0 0
Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Timepoint [14] 0 0
Part 2: Baseline to Week 96
Secondary outcome [15] 0 0
Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values
Timepoint [15] 0 0
Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96
Secondary outcome [16] 0 0
Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit
Timepoint [16] 0 0
Part 2: Baseline to Week 96

Eligibility
Key inclusion criteria
Key Part 1

* 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) (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 using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) sequences at Screening/Baseline.

Key Part 2

-Subjects who complete study treatment (BIIB033 or placebo) at Part 1/Week 72 Visit.

Key
Minimum age
18 Years
Maximum age
58 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Part 1

* 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 Part 2

* 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/02/2021
Sample size
Target
Accrual to date
Final
263
Recruitment in Australia
Recruitment state(s)
VIC
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Research Site - Box Hill
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Research Site - Clayton
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Research Site - Heidelberg
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Research Site - Parkville
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Research Site - New Lambton Heights
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Research Site - Westmead
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3128 - Box Hill
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3168 - Clayton
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3084 - Heidelberg
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3004 - Melbourne
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3050 - Parkville
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NS 2305 - New Lambton Heights
Recruitment postcode(s) [7] 0 0
2145 - Westmead
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03222973
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03222973