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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

Phase 3 Study to Evaluate Efficacy, Safety, PK, and PD of SC Natalizumab in Japanese Participants With RRMS

21

All 21 participants were Asian (100%), living in Japan, and the majority were female (14 participants [66.7%]). The mean (SD) age was 36.6 (11.63) years, with 14 participants (66.7%) < 40 years of age. The mean (SD) weight was 56.44 (7.970) kg.

A total of 21 participants were enrolled, and all received at least 1 dose of study treatment. Of the enrolled participants, 19 participants (90.5%) completed Week 24 treatment, and 12 participants (57.1%) completed Week 48 treatment.

Most of the participants in the safety population (20 participants [95.2%]) experienced at least 1 TEAE during the study. In the safety analysis set, the most common TEAEs by PT (greater than or equal to 10% of participants) were dental caries, stomatitis, COVID-19, nasopharyngitis, lymphocyte count increased, and pruritus (3 participants [14.3%] each). Of the 20 participants (95.2%) in the safety analysis set who reported any TEAEs, 9 participants (42.9%) had TEAEs with a maximum severity of mild, and 11 participants (52.4%) had TEAEs with a maximum severity of moderate. No severe TEAEs were reported.

Primary Efficacy: The LS mean (95% CI) cumulative number of new active lesions at Week 24 was 0.37 (0.18, 0.76).The upper limit of the 95% CI was lower than the prespecified threshold value. Secondary Efficacy: The LS mean (95% CI) cumulative number of new active lesions at Week 48 was 3.08 (0.69, 13.74). The proportion of participants with any new active lesions at Week 24 and Week 48 were 0.05 (1 of 20 participants) and 0.15 (2 of 13 participants), respectively. Adjusted ARRs (95% CI) at Week 24, Week 48, and Week 52 were 0.508 (0.129, 2.005), 0.462 (0.087, 2.457), and 0.456 (0.083, 2.506), respectively. Pharmacokinetics: No serum natalizumab concentrations were observed in the participants at Baseline. After Week 4, following Q4W administration of natalizumab, the mean (SD) serum trough concentrations (Ctrough) steadily increased. After Week 16, the mean [SD] Ctrough was 21.1 mg/L [16.12]) and remained relatively stable until Week 48 (24.0 mg/L [19.00]). Pharmacodynamics: The mean decrease from baseline in serum soluble VCAM-1 concentrations was relatively stable throughout the study after the SC administration of natalizumab. The mean (SD) change from baseline to Week 24 was - 236.9 microgram/mL (81.38), and to Week 48, it was -226.6 microgram/mL (83.89).

Natalizumab 300 mg SC Q4W was efficacious and well tolerated in Japanese participants with RRMS. The safety of natalizumab SC administered as self-injection or by HCP (Q4W) in Japanese participants, as observed in Study 101MS303, is consistent with the known safety profile of natalizumab. No new safety signals were observed. Overall, the results support both self-injection and HCP administration of natalizumab SC in Japanese patients with RRMS.

Nov. 14, 2025

Yes

In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

https://jrct.mhlw.go.jp/latest-detail/jRCT2051210146

Amir Hadi Maghzi

Biogen Japan Ltd.

Nihonbashi 1-chome Mitsui Building 14F, 1-4-1, Nihonbashi, Chuo-ku, Tokyo, 103-0027

japan-medinfo@biogen.com

Biogen Japan Medical Information

Biogen Japan Ltd.

Nihonbashi 1-chome Mitsui Building 14F, 1-4-1, Nihonbashi, Chuo-ku, Tokyo, 103-0027

+81-120-560-086

japan-medinfo@biogen.com

Complete

Feb. 24, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- 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 12months 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.

- Evidence of current 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), 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 enrollment or, in the opinion of the Investigator, the participant not having stabilized from a previous relapse prior to enrollment (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.

Both

Relapsing-Remitting Multiple Sclerosis

Participants will receive natalizumab 300 mg SC Q4W for 48 weeks.

Cumulative number of new active lesions on Week 24 brain MRI scans.

- Cumulative number of new active lesions on Week 48 brain MRI scans.

- Proportion of participants with any new active lesions on Week 24 and Week 48 brain MRI scans.

- Change from baseline in number of gadolinium-enhancing lesions at Week 24 and Week 48.

- The number of nonenhancing new or newly enlarging T2 hyperintense lesions at Week 24 and Week 48.

- The number of new T1 hypointense lesions at Week 24 and Week 48.

- Annualized Relapse Rate (ARR).

- Proportion of relapse-free participants at Week 24 and Week 52.

- VAS assessing the participant's global impression of their well-being at Week 24 and Week 48.

- Incidence of treatment-emergent AEs and SAEs.

- Anti-JCV antibody.

- Anti-natalizumab antibodies.

- Change in EDSS score from Baseline.

- Serum natalizumab concentrations.

- Alpha-4-integrin saturation and serum soluble VCAM-1 concentrations.

+81-6-6992-1001

Dec. 07, 2021

none