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
- Registration Number
- NCT05265728
- Lead Sponsor
- Biogen
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 21
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Natalizumab 300 mg Natalizumab Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.
- Primary Outcome Measures
Name Time Method Cumulative Number of New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans Week 24 New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions.
- Secondary Outcome Measures
Name Time Method Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48 Week 24 and Week 48 Cumulative Number of New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans Week 48 New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions.
Percentage of Participants With Any New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans Week 24 Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions.
Percentage of Participants With Any New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans Week 48 Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions.
Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48 Baseline, Week 24 and Week 48 Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 72 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.
Number of Participants With Anti-Natalizumab Antibodies Baseline up to Week 48 Number of New T1 Hypointense Lesions at Week 24 and Week 48 Week 24 and Week 48 Percentage of Relapse-Free Participants at Week 24 and Week 52 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.
Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52 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.
Number of Participants With Injection Site Reactions and Injection Reactions Baseline up to Week 72 Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48 Baseline, 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.
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 Visual Analog Scale (VAS) Score at Week 24 and Week 48 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.'
Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies Baseline up to Week 48
Trial Locations
- Locations (12)
National Center of Neurology and Psychiatry
🇯🇵Kodaira-shi, Japan
St.Marianna University Hospital
🇯🇵Kawasaki-shi, Japan
Chiba University Hospital
🇯🇵Chiba-shi, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
National Hospital Organization Hokkaido Medical Center
🇯🇵Sapporo-shi, Japan
Tohoku Medical and Pharmaceutical University Hospital
🇯🇵Sendai-shi, Japan
Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital
🇯🇵Ota-ku, Japan
The Kitasato Institute Kitasato University Hospital
🇯🇵Sagamihara-shi, Japan
Tokyo Women's Medical University Yachiyo Medical Center
🇯🇵Yachiyo-shi, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-shi, Japan
Kansai Medical University Medical Center
🇯🇵Moriguchi-shi, Japan