Clinical trial NCT05265728: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2022-03-03
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative Number of New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans
timeFrame: Week 24
Secondary outcomes:
measure: Cumulative Number of New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans
timeFrame: Week 48
measure: Percentage of Participants With Any New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans
timeFrame: Week 24
measure: Percentage of Participants With Any New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans
timeFrame: Week 48
measure: Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48
timeFrame: Baseline, Week 24 and Week 48
measure: Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Number of New T1 Hypointense Lesions at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52
timeFrame: Week 24, Week 48 and Week 52
measure: Percentage of Relapse-Free Participants at Week 24 and Week 52
timeFrame: Week 24 and Week 52
measure: Visual Analog Scale (VAS) Score at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 72
measure: Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies
timeFrame: Baseline up to Week 48
measure: Number of Participants With Injection Site Reactions and Injection Reactions
timeFrame: Baseline up to Week 72
measure: Number of Participants With Anti-Natalizumab Antibodies
timeFrame: Baseline up to Week 48
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48
timeFrame: Baseline, Week 24 and Week 48
measure: Serum Trough Concentration (Ctrough) of Natalizumab
timeFrame: Up to Week 48
measure: Serum Concentration of Natalizumab Between Day 6 and Day 8
timeFrame: Day 6 to Day 8
measure: Alpha-4 (α4)-Integrin Saturation
timeFrame: Up to Week 48
measure: Serum Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) Concentrations
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
city: Kawasaki-shi
country: Japan
facility: St.Marianna University Hospital
city: Kodaira-shi
country: Japan
facility: National Center of Neurology and Psychiatry
city: Moriguchi-shi
country: Japan
facility: Kansai Medical University Medical Center
city: Ota-ku
country: Japan
facility: Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital
city: Sagamihara-shi
country: Japan
facility: The Kitasato Institute Kitasato University Hospital
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Medical Center
city: Sendai-shi
country: Japan
facility: Tohoku Medical and Pharmaceutical University Hospital
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tsukuba-shi
country: Japan
facility: University of Tsukuba Hospital
city: Yachiyo-shi
country: Japan
facility: Tokyo Women's Medical University Yachiyo Medical Center
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: