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

Phase 3TerminatedNCT05265728

Biogen21 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (12)

Juntendo University Hospital

Bunkyō City, Japan

Chiba University Hospital

Chiba, Japan

St.Marianna University Hospital

Kawasaki-shi, Japan

National Center of Neurology and Psychiatry

Kodaira-shi, Japan

Kansai Medical University Medical Center

Moriguchi-shi, Japan

Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital

Ōta-ku, Japan

The Kitasato Institute Kitasato University Hospital

Sagamihara-shi, Japan

National Hospital Organization Hokkaido Medical Center

Sapporo, Japan

Tohoku Medical and Pharmaceutical University Hospital

Sendai, Japan

Osaka University Hospital

Suita-shi, Japan

...and 2 more locations

Outcomes

Primary Outcomes

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.

Time frame: Up to Week 24

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: At Week 48

Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48

Time frame: Baseline, Weeks 24 and 48

Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24

Time frame: At Week 24

Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48

Time frame: At Week 48

Number of New T1 Hypointense Lesions at Week 24

Time frame: At Week 24

Number of New T1 Hypointense Lesions at Week 48

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: Baseline up to Week 48

Number of Participants With Injection Site Reactions and Injection Reactions

Time frame: 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

Time frame: 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.

Time frame: Baseline, Week 24 and Week 48

Serum Trough Concentration (Ctrough) of Natalizumab

Time frame: 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.

Time frame: Between Day 6 and Day 8

Trough Alpha-4 (α4) Integrin Saturation

Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48

Serum Soluble VCAM-1 Concentrations

Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48