Clinical trial NCT04079088: Study to Evaluate Oral BIIB061 Added to Interferon-beta1 (IFN-β1) or Glatiramer Acetate in Relapsing Multiple Sclerosis (RMS)
Official title: A Multicenter, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Phase 2 Study to Evaluate the Efficacy and Safety of Oral BIIB061 as Add-On Therapy to Interferon-Beta 1 or Glatiramer Acetate Therapies in Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2019-09-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are to evaluate the safety of BIIB061 versus placebo in participants with Relapsing Multiple Sclerosis (RMS), and to evaluate the efficacy of BIIB061 to improve disability outcome versus placebo in participants with RMS.

The secondary objectives of the study are to evaluate the effects of BIIB061 versus placebo on brain magnetic resonance imaging (MRI) markers of remyelination and axon preservation in chronic Multiple Sclerosis lesions and to evaluate the effects of BIIB061 versus placebo on additional measures of improved disability outcome.

Detailed description: BIIB061's unique mechanism of action may provide a pharmacological intervention to overcome the failure of remyelination in all forms of multiple sclerosis by blocking mechanisms that prevent differentiation of oligodendrocytes progenitors.

Eligibility criteria: Key Inclusion Criteria:

* Diagnosed with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS)
* Have a Baseline Expanded Disability Status Scale (EDSS) score of 2.0 to 6.0
* Have a MS disease duration of ≤20 years from first MS symptom(s)
* Must have at least one of the following occurring within 12 months prior to

Day 1/Baseline:

(a) ≥1 clinical relapse(s) or objective disability worsening (as per treating neurologist's judgment) (b) ≥1 Gadolinium (Gd)-enhancing T1 lesion(s) on brain or spinal cord Magnetic Resonance Imaging (MRI) (c) ≥1 new T2 lesion(s) on brain or spinal cord MRI (the reference scan used to detect new T2 lesion formation has to be ≤12 months prior to Day 1/Baseline)

* Must have been taking one of the following disease-modifying therapy (DMTs) at a stable dose for at least 12 weeks prior to Day 1/Baseline:

  1. Interferon-beta1 (IFN-β1): Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif
  2. Glatiramer acetate (Copaxone or Glatopa).

     Key Exclusion Criteria:
* A documented history of clinically significant persistent neutralizing antibody against IFN-β1 (applicable only for participants entering the study with IFN-β1 as a background DMT), in the opinion of the Investigator
* 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 or a positive test result at Screening for human immunodeficiency virus
* Current hepatitis C infection (defined as positive hepatitis C virus \[HCV\] antibody and detectable HCV Ribonucleic acid (RNA)). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (United States \[US\] Centers for Disease Control and Prevention)
* Current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] or total hepatitis B core antibody \[anti-HBc\]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive hepatitis B surface antibody \[anti-HBs\]) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study
* History of systemic hypersensitivity reaction to BIIB061
* History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 12 weeks of screening
* Clinically significant (as determined by the Investigator) 12-lead ECG or laboratory assessment abnormalities
* Any condition affecting study treatment absorption (e.g., gastrectomy)
* Treatment with statins (3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) or proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors (e.g., alirocumab and evolocumab) within 8 weeks prior to Day 1/Baseline
* Inability or unwillingness to comply with study requirements
* Other unspecified reasons that, in the opinion of the Investigator or Biogen that make the participant unsuitable for enrollment.

Note: Other protocol defined inclusion/ exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First dose of study drug to end of the study (Up to Week 84)
measure: Overall Disability Response Score (ODRS) at Week 48
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Change from Baseline in Normalized Magnetization Transfer Ratio (nMTR) at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in Diffusion Tensor Imaging Radial Diffusivity (DTI-RD) at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in Normalized T1 (nT1) Intensity at Week 48
timeFrame: Baseline, Week 48
measure: Change from Baseline in T1 Hypointense Volume at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants with 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
timeFrame: Up to Week 48
measure: Percentage of Participants with 12-week Confirmed Worsening in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
timeFrame: Up to Week 48
measure: ODRS Accounting Only for 12-week Confirmed Events of Worsening and Improvement on Respective Components over the First 48 Weeks of Treatment
timeFrame: 48 weeks
measure: ODRS using 20% Threshold for T25FW over the First 48 Weeks of Treatment
timeFrame: 48 weeks
measure: ODRS using 20% Threshold for T25FW, 9HPTD, and 9HPT-ND over the First 48 Weeks of Treatment
timeFrame: 48 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: