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Study to Evaluate Oral BIIB061 Added to Interferon-beta1 (IFN-β1) in Relapsing Multiple Sclerosis (RMS)

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ClinicalTrials.gov Identifier: NCT04079088
Recruitment Status : Not yet recruiting
First Posted : September 6, 2019
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

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.


Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis Drug: Placebo Drug: BIIB061 Biological: Interferon-beta1 Phase 2

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 via blockade of receptors that prevent differentiation of oligodendrocyte progenitor cells.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Therapies in Relapsing Multiple Sclerosis
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : October 12, 2022
Estimated Study Completion Date : October 12, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Participants will receive BIIB061-matched placebo, orally once daily in addition to IFN-β1 injection for up to 72 weeks.
Drug: Placebo
Administered as specified in the treatment arm.

Biological: Interferon-beta1
Stable dose as prescribed by the physician.
Other Name: Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif

Experimental: BIIB061 Dose 1
Participants will receive BIIB061 Dose 1 orally once daily in addition to IFN-β1 injection for up to 72 weeks.
Drug: BIIB061
Administered as specified in the treatment arm.

Biological: Interferon-beta1
Stable dose as prescribed by the physician.
Other Name: Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif

Experimental: BIIB061 Dose 2
Participants will receive BIIB061 Dose 2 orally once daily in addition to IFN-β1 injection for up to 72 weeks.
Drug: BIIB061
Administered as specified in the treatment arm.

Biological: Interferon-beta1
Stable dose as prescribed by the physician.
Other Name: Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif

Experimental: BIIB061 Dose 3
Participants will receive BIIB061 Dose 3 orally once daily in addition to IFN-β1 injection for up to 72 weeks.
Drug: BIIB061
Administered as specified in the treatment arm.

Biological: Interferon-beta1
Stable dose as prescribed by the physician.
Other Name: Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: First dose of study drug to end of the study (Up to Week 84) ]
    An AE is any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  2. Overall Disability Response Score (ODRS) at Week 48 [ Time Frame: Baseline, Week 48 ]
    ODRS 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). It assesses overall changes in disability over time. The 4 individual scores are added together to get the overall score that 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 Measures :
  1. Change from Baseline in Normalized Magnetization Transfer Ratio (nMTR) at Week 48 [ Time Frame: Baseline, Week 48 ]
    Remyelination will be measured using magnetization transfer ratio (MTR) in chronic MS lesion detected on brain MRI.

  2. Change from Baseline in Diffusion Tensor Imaging Radial Diffusivity (DTI-RD) at Week 48 [ Time Frame: Baseline, Week 48 ]
    Axon and myelin preservation will be measured using DTI-RD in chronic MS lesions detected on brain MRI.

  3. Percentage of Participants with 12-week Confirmed Improvement in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND [ Time Frame: Up to Week 48 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  4. Percentage of Participants with 12-week Confirmed Worsening in at Least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND [ Time Frame: Up to Week 48 ]
    EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist. The T25FW is a quantitative mobility and leg function performance test based on a timed walk over 25 feet. The score for the T25FW is averaged between two completed trials. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

  5. ODRS Accounting Only for 12-week Confirmed Events of Worsening and Improvement on Respective Components over the First 48 Weeks of Treatment [ Time Frame: 48 weeks ]
    ODRS is a multicomponent score based on 4 components: EDSS, T25FW, 9HPT-D, and 9HPT-ND. It assesses overall changes in disability over time. The 4 individual scores are added together to get the overall score that 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.

  6. ODRS using 20% Threshold for T25FW over the First 48 Weeks of Treatment [ Time Frame: 48 weeks ]
    ODRS is a multicomponent score based on 4 components: EDSS, T25FW, 9HPT-D, and 9HPT-ND. It assesses overall changes in disability over time. The 4 individual scores are added together to get the overall score that 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 a 20% and 15% change from baseline respectively. 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.

  7. ODRS using 20% Threshold for T25FW, 9HPTD, and 9HPT-ND over the First 48 Weeks of Treatment [ Time Frame: 48 weeks ]
    ODRS is a multicomponent score based on 4 components: EDSS, T25FW, 9HPT-D, and 9HPT-ND. It assesses overall changes in disability over time. The 4 individual scores are added together to get the overall score that 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 a 20% change from baseline. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  1. ≥1 clinical relapse(s) or objective disability worsening (as per treating neurologist's judgment)
  2. ≥1 Gadolinium (Gd)-enhancing T1 lesion(s) on brain or spinal cord Magnetic Resonance Imaging (MRI)
  3. ≥1 new T2 lesion(s) on brain or spinal cord MRI

    • 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:

(a) Interferon-beta1 (IFN-β1): Avonex, Plegridy, Betaferon/Betaseron, Extavia, or Rebif.

Key Exclusion Criteria:

  • A documented history of clinically significant persistent neutralizing antibody against IFN-β, 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 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)
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04079088


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT04079088    
Other Study ID Numbers: 231MS201
2019-001847-28 ( EudraCT Number )
First Posted: September 6, 2019    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
URL: http://www.biogenclinicaldatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Interferon-beta
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs