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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Natalizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Natalizumab 300 mg<br>Participants will receive natalizumab 300 mg SC Q4W for 48 weeks. | Drug: Natalizumab<br>* Administered as specified in the treatment arm<br>* Other names: BG00002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans | New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Number of New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans | New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions. | Week 48 | 
| Percentage of Participants With Any New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans | Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions. | Week 24 | 
| Percentage of Participants With Any New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans | Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions. | Week 48 | 
| Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48 |  | Baseline, Week 24 and Week 48 | 
| Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48 |  | Week 24 and Week 48 | 
| Number of New T1 Hypointense Lesions at Week 24 and Week 48 |  | Week 24 and Week 48 | 
| Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 | A multiple sclerosis (MS) relapse is 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. ARR is defined as the total number of relapses divided by the total participant-time at risk of relapse. | Week 24, Week 48 and Week 52 | 
| Percentage of Relapse-Free Participants at Week 24 and Week 52 | An MS relapse is 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. | 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 will be assessed with a VAS. The instrument ranges from 0 to 100 millimeter (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent.' | Week 24 and Week 48 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An adverse event (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. A treatment-emergent AE is 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. A serous adverse event (SAE) is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. | Baseline up to Week 72 | 
| Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies |  | Baseline up to Week 48 | 
| Number of Participants With Injection Site Reactions and Injection Reactions |  | Baseline up to Week 72 | 
| Number of Participants With 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 measures disability status on a scale ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]), with higher scores indicating more disability. | Baseline, Week 24 and Week 48 | 
| Serum Trough Concentration (Ctrough) of Natalizumab |  | Up to Week 48 | 
| Serum Concentration of Natalizumab Between Day 6 and Day 8 |  | Day 6 to Day 8 | 
| Alpha-4 (α4)-Integrin Saturation |  | Up to Week 48 | 
| Serum Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) Concentrations |  | Up to Week 48 |