Clinical trial NCT03222973: Efficacy and Safety of BIIB033 (Opicinumab) as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Remyelination
Re-myelination
DMT
LINGO-1
Anti-LINGO-1
Opicinumab
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-07-19
Enrollment: 263
Sex: ALL
Minimum age (years): 18
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria: 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) (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.

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 Exclusion Criteria: 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

Primary outcomes:
measure: Part 1: Overall Response Score
timeFrame: Part 1: Baseline to Week 72
measure: Part 2: Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part 2: Baseline to Week 169
Secondary outcomes:
measure: 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
timeFrame: Part 1: Baseline to Week 72
measure: 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)
timeFrame: Part 1: Baseline to Week 72
measure: 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
timeFrame: Part 1: Baseline to Week 72
measure: 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)
timeFrame: Part 1: Baseline to Week 72
measure: 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)
timeFrame: Part 1: Baseline to Week 72
measure: Part 2: Overall Response Score
timeFrame: Part 2: Baseline to Week 96
measure: 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
timeFrame: Part 2: Baseline to Week 108
measure: 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
timeFrame: Part 2: Baseline to Week 108
measure: 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
timeFrame: Part 2: Baseline to Week 96
measure: 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
timeFrame: Part 2: Baseline to Week 108
measure: 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)
timeFrame: Part 2: Baseline to Week 108
measure: Part 2: Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values
timeFrame: Part 2: Baseline to Week 96
measure: Part 2: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Values
timeFrame: Part 2: Baseline to Week 96
measure: Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Part 2: Baseline to Week 96
measure: Part 2: Percentage of Participants With Potentially Clinically Significant Abnormal Weight Values
timeFrame: Part 2: Baseline, Week 12, 24, 36, 48, 72 and 96
measure: Part 2: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Score at Any Post-Baseline Visit
timeFrame: Part 2: Baseline to Week 96
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Research Site
state: Alabama
city: Gilbert
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state: Arizona
city: Berkeley
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country: France
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city: Nimes
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country: Germany
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Netherlands
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city: Bydgoszcz
country: Poland
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city: Gdansk
country: Poland
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city: Katowice
country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Zabrze
country: Poland
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city: Salt
country: Spain
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state: Girona
city: Majadahonda
country: Spain
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state: Madrid
city: Barakaldo
country: Spain
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state: Vizcaya
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Aarau
country: Switzerland
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Bern
country: Switzerland
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city: Lugano
country: Switzerland
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city: Zurich
country: Switzerland
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
state: Devon
city: Plymouth
country: United Kingdom
facility: Research Site
state: Devon
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Salford
country: United Kingdom
facility: Research Site
state: Greater Manchester
city: Liverpool
country: United Kingdom
facility: Research Site
state: Merseyside
city: Nottingham
country: United Kingdom
facility: Research Site
state: Nottinghamshire
city: Oxford
country: United Kingdom
facility: Research Site
state: Oxfordshire
city: Glasgow
country: United Kingdom
facility: Research Site
state: Strathclyde
city: Newcastle Upon Tyne
country: United Kingdom
facility: Research Site
state: Tyne & Wear
city: Leeds
country: United Kingdom
facility: Research Site
state: West Yorkshire
city: Brighton
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.