Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT01416155
• Recruitment Status: Completed
• First Posted: August 12, 2011
• Results First Posted: January 14, 2016
• Last Update Posted: January 14, 2016
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

The primary objective of the study is to further evaluate the long-term safety and tolerability profiles of BG00002 (natalizumab) in Japanese participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objective of this study is to further evaluate the long-term efficacy profile of BG00002 in Japanese participants with RRMS.

Condition or disease	Intervention/treatment	Phase
Relapsing-Remitting Multiple Sclerosis; Multiple Sclerosis	Drug: natalizumab	Phase 2

Detailed Description:

This is a multicenter, long-term, open-label, extension study in participants who have successfully completed Study 101MS203 (NCT01440101).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term, Open-Label, Multicenter, Extension Study to Evaluate Safety and Efficacy of BG00002 in Japanese Subjects With Relapsing-Remitting Multiple Sclerosis
• Study Start Date: October 2010
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: natalizumab; 300 mg intravenous (IV) infusions of natalizumab every 4 weeks until product is approved in Japan or development is discontinued in Japan, whichever comes first.	Drug: natalizumab; Other Names: Tysabri; BG00002

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs [ Time Frame: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months ]
   An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the subject at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
2. Number of Participants With Serum Antibodies to Natalizumab [ Time Frame: Day 1 up to approximately 50 months ]
   Negative is defined as negative for antibodies at all post-baseline results. Transient positivity is defined as only 1 positive result. Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.

Secondary Outcome Measures :

1. Adjusted Annualized Relapse Rate [ Time Frame: Day 1 up to approximately 50 months ]
   Clinical relapses are defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurological findings upon examination by the neurologist. The annualized relapse rate is calculated overall as the total number of relapses experienced in the study divided by the number of days followed in the study, and the ratio multiplied by 365. Obtained from a Poisson regression model, adjusted for the baseline relapse rate from study 101MS203 (NCT01440101).
2. Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 [ Time Frame: Day 1 up to Week 192 ]
   The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and any authorizations required by local law.
• Subjects who participated in and completed all protocol-related evaluations through Week 24 of Study 101MS203 (NCT01440101).
• Subjects participating in study 101MS204 (NCT01416155) participated either in the open label pharmacokinetics-pharmacodynamics study or placebo-controlled study of natalizumab 300 mg q4wks (parts A and B of study 101MS203, respectively).
• Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 12 weeks after their last dose of study treatment.
• Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta [IFNβ] and long-term systemic corticosteroids) for the duration of the study.

Key Exclusion Criteria Medical History

• Any significant change in medical history since Study 101MS203 (NCT01440101), including laboratory tests, or current clinically important condition that in the opinion of the Investigator would have excluded the subject's participation in the previous study. The Investigator must re-review the subject's medical fitness for participation and consider diseases that would preclude treatment.
• Subjects from Study 101MS203 (NCT01440101) who discontinued study treatment due to an adverse event.
• Subjects who are determined to be persistently positive for anti-BG0002 antibodies based on prior testing.

Treatment History

• Treatment with any of the following medications between last dose of study treatment in Study 101MS203 (NCT01440101) and the start of this study: intravenous immunoglobulin (IVIg), plasmapheresis, cytapheresis, immunosuppressant medications (e.g., mitoxantrone, azathioprine, cyclophosphamide, methotrexate, cyclosporine, FTY720), immunomodulatory medications (including IFNβ and glatiramer acetate [GA]) total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, any murine protein, any other therapeutic monoclonal antibody, or any 4-aminopyridine or related products.

Miscellaneous

• For female subjects, unless postmenopausal for at least 1 year or surgically sterile (does not include tubal ligation), unwillingness to practice effective contraception, as defined by the Investigator, during the study. Women considering becoming pregnant while on study are to be excluded.
• Female subjects who are currently pregnant or breast feeding, including subjects whose pregnancy test is positive at Week 0.
• Unwillingness or inability to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the study protocol.
• Subjects with any other condition, clinical finding, or reason that in the opinion of the Investigator and/or the Sponsor makes the subject unsuitable for enrollment into the study.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

Japan

Research Site

Sapporo, Hokkaido, Japan, 060-8648

Research Site

Sapporo, Hokkaido, Japan, 063-0005

Research Site

Tsukuba, Ibaraki, Japan, 305-8576

Research Site

Morioka, Iwate, Japan, 020-8505

Research Site

Yokohama, Kanagawa, Japan, 232-0024

Research Site

Sendai, Miyagi, Japan, 980-8574

Research Site

Suita, Osaka, Japan, 565-0871

Research Site

Kawagoe, Saitama, Japan, 350-8550

Research Site

Tokorozawa, Saitama, Japan, 359-8513

Research Site

Bunkyo-ku, Tokyo, Japan, 113-8431

Research Site

Bunkyo-ku, Tokyo, Japan, 113-8519

Research Site

Kodaira, Tokyo, Japan, 187-8551

Research Site

Ota-ku, Tokyo, Japan, 145-0065

Research Site

Ube, Yamaguchi, Japan, 755-8505

Research Site

Chiba, Japan, 260-8677

Research Site

Fukuoka, Japan, 812-8582

Research Site

Hiroshima, Japan, 734-8551

Research Site

Kyoto, Japan, 604-8453

Research Site

Kyoto, Japan, 606-8507

Research Site

Kyoto, Japan, 616-8255

Research Site

Niigata, Japan, 951-8520

Research Site

Osaka, Japan, 556-0016

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Ling Y, Torii S, Lucas N, Kuesters G, Steiner D, Tibung JT; Natalizumab Trial Principal Investigators. Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial. Neurol Ther. 2017 Jun;6(1):39-55. doi: 10.1007/s40120-016-0059-z. Epub 2016 Dec 5.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT01416155
• Other Study ID Numbers: 101MS204
• First Posted: August 12, 2011
• Results First Posted: January 14, 2016
• Last Update Posted: January 14, 2016
• Last Verified: December 2015

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Natalizumab; Immunologic Factors; Physiological Effects of Drugs