A Phase 3 interventional study of Natalizumab in Multiple Sclerosis, Relapsing-Remitting, sponsored by Biogen. Terminated at 12 sites in Japan. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-11-25.
Sponsored by Biogen · Phase 3, Interventional, and Treatment
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.
602 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 80 are open to participants now.
This study's enrollment of 21 is below the median of 72 across 429 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.
Browse Multiple Sclerosis, Relapsing-Remitting studies →Biogen is the lead sponsor of 494 studies on the registry; 22 are open to participants now.
Of its 98 completed or terminated interventional studies of FDA-regulated products, 49 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol specified Inclusion/Exclusion criteria may apply.
Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.
Drug: Natalizumab
Administered as specified in the treatment arm
Also known as: BG00002, Tysabri
Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans
New active lesions were defined as the sum of gadolinium (Gd)-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 24 weeks.
Time frame: Up to Week 24
Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 48 weeks.
Time frame: Up to Week 48
Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans
New active lesions were defined as the sum of gadolinium-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
Time frame: At Week 24
Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
Time frame: At Week 48
Change From Baseline in Number of Gd-Enhancing Lesions at Week 24 and Week 48
Time frame: Baseline, Weeks 24 and 48
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24
Time frame: At Week 24
Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48
Time frame: At Week 48
Number of New T1 Hypointense Lesions at Week 24
Time frame: At Week 24
Number of New T1 Hypointense Lesions at Week 48
Time frame: At Week 48
Annualized Relapse Rate (ARR) at Week 24, Week 48 and Week 52
ARR is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.
Time frame: At Week 24, Week 48 and Week 52
Proportion of Relapse-Free Participants at Week 24 and Week 52
A multiple sclerosis (MS) relapse was 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: At 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 was assessed with a VAS. The instrument ranges from 0 to 100 millimeters (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent'. Higher scores indicates a better health state.
Time frame: At Week 24 and Week 48
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as 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.
Time frame: From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies
Time frame: Baseline up to Week 48
Number of Participants With Injection Site Reactions and Injection Reactions
Time frame: From first dose of study drug through 84 days after the last dose of study drug (up to Week 60)
Percentage of Participants With Positive Anti-Natalizumab Antibodies
Time frame: Baseline up to Week 48
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 24 and Week 48
The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability. A negative change from baseline indicates an improvement in the disability.
Time frame: Baseline, Week 24 and Week 48
Serum Trough Concentration (Ctrough) of Natalizumab
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Serum Concentration of Natalizumab Between Day 6 and Day 8
One blood sample was collected between Day 6 and Day 8.
Time frame: Between Day 6 and Day 8
Trough Alpha-4 (α4) Integrin Saturation
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Serum Soluble VCAM-1 Concentrations
Time frame: Pre-dose at Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
Participants were enrolled at multiple investigative sites in Japan from 26 April 2022 to 29 June 2023.
| Milestone | Natalizumab |
|---|---|
| Started | 21 |
| Completed | 13 |
| Not completed | 8 |
| Withdrew: Adverse event | 1 |
| Withdrew: Study terminated by sponsor | 5 |
| Withdrew: Withdrawal by subject | 2 |
New active lesions were defined as the sum of gadolinium (Gd)-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 24 weeks.
| number of lesions | Natalizumab |
|---|---|
| Part 1: Cumulative Number of New Active Lesions up to Week 24 Identified Using Brain Magnetic Resonance Imaging (MRI) Scans | 0.4 ± 0.60 |
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions over a period of 48 weeks.
| number of lesions | Natalizumab |
|---|---|
| Part 2: Cumulative Number of New Active Lesions up to Week 48 Identified Using Brain MRI Scans | 3.1 ± 8.47 |
New active lesions were defined as the sum of gadolinium-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
| proportion of participants | Natalizumab |
|---|---|
| Part 1: Proportion of Participants With Any New Active Lesions at Week 24 Identified Using Brain MRI Scans | 0.05 |
New active lesions were defined as the sum of Gd-enhancing lesions and non-enhancing new or newly enlarging T2 hyperintense lesions.
| proportion of participants | Natalizumab |
|---|---|
| Part 2: Proportion of Participants With Any New Active Lesions at Week 48 Identified Using Brain MRI Scans | 0.15 |
| number of lesions | Natalizumab |
|---|---|
| Baseline | 0.5 ± 1.44 |
| Change at Week 24 | -0.6 ± 1.47 |
| Change at Week 48 | -0.7 ± 1.72 |
| number of lesions | Natalizumab |
|---|---|
| Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 24 | 0.3 ± 1.34 |
| number of lesions | Natalizumab |
|---|---|
| Number of Non-enhancing New or Newly Enlarging T2 Hyperintense Lesions at Week 48 | 2.1 ± 6.64 |
| number of lesions | Natalizumab |
|---|---|
| Number of New T1 Hypointense Lesions at Week 24 | 0.0 ± 0.0 |
| number of lesions | Natalizumab |
|---|---|
| Number of New T1 Hypointense Lesions at Week 48 | 0.2 ± 0.60 |
ARR is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years. ARR was analyzed using negative binomial regression model.
| relapses per participant-year | Natalizumab |
|---|---|
| Week 24 | 0.508 (0.129 to 2.005) |
| Week 48 | 0.462 (0.087 to 2.457) |
| Week 52 | 0.456 (0.083 to 2.506) |
A multiple sclerosis (MS) relapse was 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.
| proportion of participants | Natalizumab |
|---|---|
| Week 24 | 0.8521 |
| Week 52 | 0.8521 |
The participant's global impression of his/her well-being was assessed with a VAS. The instrument ranges from 0 to 100 millimeters (mm), where a score of 0 denotes 'poor' and a score of 100 denotes 'excellent'. Higher scores indicates a better health state.
| mm | Natalizumab |
|---|---|
| Week 24 | 71.0 ± 22.35 |
| Week 48 | 61.5 ± 22.02 |
An 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is defined as 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.
| percentage of participants | Natalizumab |
|---|---|
| TEAEs | 95.2 |
| Serious TEAEs | 4.8 |
| percentage of participants | Natalizumab |
|---|---|
| Percentage of Participants With Positive Anti-John Cunningham Virus (Anti-JCV) Antibodies | 57.1 |
| Participants | Natalizumab |
|---|---|
| Injection Site Reactions | 3 (NA to NA) |
| Injection Reactions | 2 (NA to NA) |
| percentage of participants | Natalizumab |
|---|---|
| Percentage of Participants With Positive Anti-Natalizumab Antibodies | 4.8 |
The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability. A negative change from baseline indicates an improvement in the disability.
| score on a scale | Natalizumab |
|---|---|
| Baseline | 1.83 ± 1.544 |
| Change at Week 24 | 0.02 ± 0.536 |
| Change at Week 48 | -0.13 ± 0.352 |
| milligrams per liter (mg/L) | Natalizumab |
|---|---|
| Baseline | 0.0 ± 0.00 |
| Week 4 | 10.6 ± 6.59 |
| Week 8 | 15.1 ± 10.11 |
| Week 12 | 18.3 ± 13.22 |
| Week 16 | 21.1 ± 16.12 |
| Week 20 | 20.7 ± 15.13 |
| Week 24 | 23.6 ± 17.77 |
| Week 28 | 22.2 ± 14.01 |
| Week 32 | 20.0 ± 15.70 |
| Week 36 | 22.1 ± 13.95 |
| Week 40 | 19.5 ± 15.31 |
| Week 44 | 22.5 ± 14.76 |
| Week 48 | 24.0 ± 19.00 |
One blood sample was collected between Day 6 and Day 8.
| mg/L | Natalizumab |
|---|---|
| Serum Concentration of Natalizumab Between Day 6 and Day 8 | 29.8 ± 15.07 |
| percentage | Natalizumab |
|---|---|
| Baseline | 4.9 ± 4.99 |
| Week 4 | 81.9 ± 18.31 |
| Week 8 | 82.6 ± 20.85 |
| Week 12 | 82.8 ± 20.22 |
| Week 16 | 87.3 ± 19.52 |
| Week 20 | 87.0 ± 17.10 |
| Week 24 | 87.1 ± 23.59 |
| Week 28 | 86.4 ± 21.97 |
| Week 32 | 87.1 ± 26.46 |
| Week 36 | 82.6 ± 23.93 |
| Week 40 | 84.6 ± 26.27 |
| Week 44 | 83.3 ± 25.22 |
| Week 48 | 80.1 ± 24.98 |
| micrograms per liter (µg/L) | Natalizumab |
|---|---|
| Baseline | 468.9 ± 80.90 |
| Week 4 | 237.8 ± 66.29 |
| Week 8 | 248.2 ± 86.47 |
| Week 12 | 239.8 ± 77.96 |
| Week 16 | 231.8 ± 70.76 |
| Week 20 | 236.0 ± 71.22 |
| Week 24 | 237.4 ± 80.38 |
| Week 28 | 229.1 ± 80.47 |
| Week 32 | 238.1 ± 86.11 |
| Week 36 | 243.1 ± 105.46 |
| Week 40 | 235.6 ± 80.59 |
| Week 44 | 242.0 ± 72.06 |
| Week 48 | 244.1 ± 87.07 |
Collected over Deaths were assessed up to 76 weeks; Adverse Events were assessed up to Week 60. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Natalizumab | 0/21 (0%) | 1/21 (4.8%) | 17/21 (81%) |
| Event | Natalizumab |
|---|---|
| Progressive multifocal leukoencephalopathyInfections and infestations | 1/21 |
| Event | Natalizumab |
|---|---|
| Dental cariesGastrointestinal disorders | 3/21 |
| StomatitisGastrointestinal disorders | 3/21 |
| Covid-19Infections and infestations | 3/21 |
| NasopharyngitisInfections and infestations | 3/21 |
| Lymphocyte count increasedInvestigations | 3/21 |
| PruritusSkin and subcutaneous tissue disorders | 3/21 |
| Injection site reactionGeneral disorders | 2/21 |
| Drug-induced liver injuryHepatobiliary disorders | 2/21 |
| PharyngitisInfections and infestations | 2/21 |
| Upper respiratory tract infectionInfections and infestations | 2/21 |
Full analysis set (FAS) included all participants who had received at least 1 study treatment injection and had at least 1 post baseline efficacy assessment.
| Age, Continuous(years) | Natalizumab |
|---|---|
| Mean | 36.6 ± 11.63 |
| Sex: Female, Male(Participants) | Natalizumab |
|---|---|
| Female | 14 |
| Male | 7 |
| Ethnicity (NIH/OMB)(Participants) | Natalizumab |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 21 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Natalizumab |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 21 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Multiple Sclerosis, Relapsing-Remitting→
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