A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Natalizumab (BG00002) Administered Subcutaneously to Japanese Participants With Relapsing-Remitting Multiple Sclerosis

A Single-Arm, Open-Label, Phase 3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Natalizumab (BG00002) Administered to Japanese Participants With Relapsing-Remitting Multiple Sclerosis Via a Subcutaneous Route of Administration

The primary objective of this study is to evaluate the efficacy of natalizumab 300 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) administrations up to 24 weeks in Japanese participants with relapsing-remitting multiple sclerosis (RRMS).

The secondary objectives of the study are to evaluate other clinical and magnetic resonance imaging (MRI) measures of efficacy of natalizumab 300 mg SC Q4W administrations in Japanese participants with RRMS, to evaluate the safety, tolerability, and immunogenicity of natalizumab 300 mg SC Q4W administrations up to 48 weeks in Japanese participants with RRMS, to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of natalizumab 300 mg SC Q4W administrations up to 24 weeks and for an additional 24 weeks in Japanese participants with RRMS.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Natalizumab

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyō City, Japan, 113-8431
    • Juntendo University Hospital
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Kawasaki-shi, Japan, 216-8511
    • St.Marianna University Hospital
  • Kodaira-shi, Japan, 187-8551
    • National Center of Neurology and Psychiatry
  • Moriguchi-shi, Japan, 570-8507
    • Kansai Medical University Medical Center
  • Sagamihara-shi, Japan, 252-0375
    • The Kitasato Institute Kitasato University Hospital
  • Sapporo, Japan, 063-0005
    • National Hospital Organization Hokkaido Medical Center
  • Sendai, Japan, 983-8512
    • Tohoku Medical and Pharmaceutical University Hospital
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
  • Tsukuba, Japan, 305-8576
    • University of Tsukuba Hospital
  • Yachiyo-shi, Japan, 276-8524
    • Tokyo Women's Medical University Yachiyo Medical Center
  • Ōta-ku, Japan, 145-0065
    • Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must have had a diagnosis of RRMS, as defined by the revised 2017 McDonald's criteria. All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the investigator.
• Must have had an EDSS score between 0.0 and 5.5, inclusive.
• Must have had screening MRI or documentation of an MRI within the participant's medical record within 12 months of the screening visit that revealed 3 or more T2 hyperintense lesions consistent with MS.
• Was born in Japan, and biological parents and grandparents were of Japanese origin.

Key Exclusion Criteria:

• Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to Screening, between screening and baseline visit, or at baseline visit, including but not limited to a fever (temperature > 37.5 degrees Celsius [°C]), new and persistent cough, breathlessness, or loss of taste and/or smell.
• Have close contact within 14 days prior to Day 1 with a SARS-CoV-2 positive individual.
• Diagnosis of primary progressive MS or secondary progressive MS.
• An MS exacerbation (relapse) within 30 days prior to enrolment or, in the opinion of the investigator, the participant not having stabilized from a previous relapse prior to enrolment (Day 1).
• The participant is unable to have a brain MRI scan (e.g., a participant with a metal clip to repair a cerebral aneurysm).
• Previous exposure to natalizumab.

Note: Other protocol specified Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Natalizumab; Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.	Drug: Natalizumab; Administered as specified in the treatment arm; Other Names: Tysabri; BG00002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans	New active lesions were defined as the sum of gadolinium (Gd)-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 24 weeks.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans	New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 48 weeks.	Up to Week 48
Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans	New active lesions were defined as the sum of gadolinium-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.	At Week 24
Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans	New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.	At Week 48
Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48		Baseline, Weeks 24 and 48
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24		At Week 24
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48		At Week 48
Number of New T1 Hypointense Lesions at Week 24		At Week 24
Number of New T1 Hypointense Lesions at Week 48		At Week 48
Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52	ARR is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.	At Week 24, Week 48 and Week 52
Proportion of Relapse-Free Participants at Week 24 and Week 52	A multiple sclerosis (MS) relapse was defined as the onset of new or recurrent neurological symptoms lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination, and not explained solely by non-MS processes such as fever, infection, severe stress, or drug toxicity.	At Week 24 and Week 52
Visual Analog Scale (VAS) Score at Week 24 and Week 48	The participant's global impression of his/her well-being was assessed with a VAS. The instrument ranges from 0 to 100 millimeters (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent'. Higher scores indicates a better health state.	At Week 24 and Week 48
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be 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. A TEAE is defined as any AE that has an onset date and time that is on or after the date and time of the first dose of study treatment, or that has worsened after the date and time of the first dose of study treatment through 84 days after the last dose of study treatment.	From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies		Baseline up to Week 48
Number of Participants With Injection Site Reactions and Injection Reactions		From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Percentage of Participants With Positive Anti-Natalizumab Antibodies		Baseline up to Week 48
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48	The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability. A negative change from baseline indicates an improvement in the disability.	Baseline, Week 24 and Week 48
Serum Trough Concentration (Ctrough) of Natalizumab		Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Serum Concentration of Natalizumab Between Day 6 and Day 8	One blood sample was collected between Day 6 and Day 8.	Between Day 6 and Day 8
Trough Alpha-4 (α4) Integrin Saturation		Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Serum Soluble VCAM-1 Concentrations		Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Actual): January 18, 2024
• Study Completion (Actual): May 27, 2024

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Natalizumab
• Other Study ID Numbers: 101MS330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes