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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05265728
• Other study ID #: 101MS330
• Status: Terminated
• Phase: Phase 3
• Start date: April 26, 2022
• Est. completion date: May 27, 2024

Study information

• Verified date: May 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: May 27, 2024
• Est. primary completion date: January 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Natalizumab
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Japan	Juntendo University Hospital	Bunkyo-ku
Japan	Chiba University Hospital	Chiba-shi
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	Ota-ku
Japan	The Kitasato Institute Kitasato University Hospital	Sagamihara-shi
Japan	National Hospital Organization Hokkaido Medical Center	Sapporo-shi
Japan	Tohoku Medical and Pharmaceutical University Hospital	Sendai-shi
Japan	Osaka University Hospital	Suita-shi
Japan	University of Tsukuba Hospital	Tsukuba-shi
Japan	Tokyo Women's Medical University Yachiyo Medical Center	Yachiyo-shi

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48		Baseline, Week 24 and Week 48
Secondary	Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48		Week 24 and Week 48
Secondary	Number of New T1 Hypointense Lesions at Week 24 and Week 48		Week 24 and Week 48
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies		Baseline up to Week 48
Secondary	Number of Participants With Injection Site Reactions and Injection Reactions		Baseline up to Week 72
Secondary	Number of Participants With Anti-Natalizumab Antibodies		Baseline up to Week 48
Secondary	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
Secondary	Serum Trough Concentration (Ctrough) of Natalizumab		Up to Week 48
Secondary	Serum Concentration of Natalizumab Between Day 6 and Day 8		Day 6 to Day 8
Secondary	Alpha-4 (a4)-Integrin Saturation		Up to Week 48
Secondary	Serum Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) Concentrations		Up to Week 48