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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01416155
First received: March 24, 2011
Last updated: December 10, 2015
Last verified: December 2015
  Purpose
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 Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis
Drug: natalizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serum Antibodies to Natalizumab [ Time Frame: Day 1 up to approximately 50 months ] [ Designated as safety issue: Yes ]
    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:
  • Adjusted Annualized Relapse Rate [ Time Frame: Day 1 up to approximately 50 months ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 97
Study Start Date: October 2010
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01416155

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

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01416155     History of Changes
Other Study ID Numbers: 101MS204 
Study First Received: March 24, 2011
Results First Received: December 10, 2015
Last Updated: December 10, 2015
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency (PMDA)

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
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

ClinicalTrials.gov processed this record on December 02, 2016