Back to resultsA Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Natalizumab (BG00002) Administered Subcutaneously to Japanese Participants With Relapsing-Remitting Multiple Sclerosis
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Active
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Natalizumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting
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.
Sites / Locations
- Juntendo University Hospital
- Chiba University Hospital
- St.Marianna University Hospital
- National Center of Neurology and Psychiatry
- Kansai Medical University Medical Center
- Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital
- The Kitasato Institute Kitasato University Hospital
- National Hospital Organization Hokkaido Medical Center
- Tohoku Medical and Pharmaceutical University Hospital
- Osaka University Hospital
- University of Tsukuba Hospital
- Tokyo Women's Medical University Yachiyo Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Natalizumab 300 mg
Arm Description
Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48
Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48
Number of New T1 Hypointense Lesions at 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.
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.
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.'
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.
Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies
Number of Participants With Injection Site Reactions and Injection Reactions
Number of Participants With Anti-Natalizumab Antibodies
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.
Serum Trough Concentration (Ctrough) of Natalizumab
Serum Concentration of Natalizumab Between Day 6 and Day 8
Alpha-4 (α4)-Integrin Saturation
Serum Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) Concentrations
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05265728
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 26, 2022 (Actual)
Primary Completion Date
January 18, 2024 (Anticipated)
Study Completion Date
June 6, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Natalizumab 300 mg
Arm Type
Experimental
Arm Description
Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Natalizumab
Other Intervention Name(s)
BG00002
Intervention Description
Administered as specified in the treatment arm
Primary Outcome Measure Information:
Title
Cumulative Number of New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans
Description
New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Cumulative Number of New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans
Description
New active lesions are defined as sum of gadolinium-enhancing lesions and nonenhancing new or newly enlarging T2 hyperintense lesions.
Time Frame
Week 48
Title
Percentage of Participants With Any New Active Lesions on Week 24 Brain Magnetic Resonance Imaging (MRI) Scans
Description
Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions.
Time Frame
Week 24
Title
Percentage of Participants With Any New Active Lesions on Week 48 Brain Magnetic Resonance Imaging (MRI) Scans
Description
Any new active lesions include gadolinium-enhancing lesions or nonenhancing new or newly enlarging T2 hyperintense lesions.
Time Frame
Week 48
Title
Change from Baseline in Number of Gadolinium-Enhancing Lesions at Week 24 and Week 48
Time Frame
Baseline, Week 24 and Week 48
Title
Number of Nonenhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 and Week 48
Time Frame
Week 24 and Week 48
Title
Number of New T1 Hypointense Lesions at Week 24 and Week 48
Time Frame
Week 24 and Week 48
Title
Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52
Description
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.
Time Frame
Week 24, Week 48 and Week 52
Title
Percentage of Relapse-Free Participants at Week 24 and Week 52
Description
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.
Time Frame
Week 24 and Week 52
Title
Visual Analog Scale (VAS) Score at Week 24 and Week 48
Description
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.'
Time Frame
Week 24 and Week 48
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Week 72
Title
Number of Participants With Anti-John Cunningham Virus (Anti-JCV) Antibodies
Time Frame
Baseline up to Week 48
Title
Number of Participants With Injection Site Reactions and Injection Reactions
Time Frame
Baseline up to Week 72
Title
Number of Participants With Anti-Natalizumab Antibodies
Time Frame
Baseline up to Week 48
Title
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48
Description
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.
Time Frame
Baseline, Week 24 and Week 48
Title
Serum Trough Concentration (Ctrough) of Natalizumab
Time Frame
Up to Week 48
Title
Serum Concentration of Natalizumab Between Day 6 and Day 8
Time Frame
Day 6 to Day 8
Title
Alpha-4 (α4)-Integrin Saturation
Time Frame
Up to Week 48
Title
Serum Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) Concentrations
Time Frame
Up to Week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Juntendo University Hospital
City
Bunkyo-ku
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Chiba University Hospital
City
Chiba-shi
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
St.Marianna University Hospital
City
Kawasaki-shi
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
National Center of Neurology and Psychiatry
City
Kodaira-shi
ZIP/Postal Code
187-8551
Country
Japan
Facility Name
Kansai Medical University Medical Center
City
Moriguchi-shi
ZIP/Postal Code
570-8507
Country
Japan
Facility Name
Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Ebara Hospital
City
Ota-ku
ZIP/Postal Code
145-0065
Country
Japan
Facility Name
The Kitasato Institute Kitasato University Hospital
City
Sagamihara-shi
ZIP/Postal Code
252-0375
Country
Japan
Facility Name
National Hospital Organization Hokkaido Medical Center
City
Sapporo-shi
ZIP/Postal Code
063-0005
Country
Japan
Facility Name
Tohoku Medical and Pharmaceutical University Hospital
City
Sendai-shi
ZIP/Postal Code
983-8512
Country
Japan
Facility Name
Osaka University Hospital
City
Suita-shi
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba-shi
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Tokyo Women's Medical University Yachiyo Medical Center
City
Yachiyo-shi
ZIP/Postal Code
276-8524
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Learn more about this trial
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
We'll reach out to this number within 24 hrs