Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS). (REFINE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT01405820
First received: July 14, 2011
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

The primary objective of this study is to explore the effects of multiple regimens of natalizumab on disease activity and safety in participants with relapsing-remitting Multiple Sclerosis (RRMS).


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: BG00002 (Natalizumab) IV
Drug: BG00002 (Natalizumab) SC
Drug: IV Placebo
Drug: SC Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis.

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Cumulative number of combined unique active lesions [ Time Frame: Baseline and Weeks 12, 24, 36, 48 and 60 ] [ Designated as safety issue: No ]
    Cumulative number of combined unique active lesions (sum of the number of new gadolinium (Gd)-enhancing lesions and new or newly enlarging T2 hyperintense lesions not associated with Gd-enhancement on T1 weighted scans) based on brain magnetic resonance imaging (MRI) scans at Weeks 12, 24, 36, 48 and 60.

  • Number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; expected 72 weeks. ] [ Designated as safety issue: Yes ]

Enrollment: 291
Study Start Date: August 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Natalizumab 300 mg IV every 4 weeks
Participants will receive intravenous (IV) natalizumab 300 mg every 4 weeks for 60 weeks.
Drug: BG00002 (Natalizumab) IV
Natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Experimental: Natalizumab 300 mg SC every 4 weeks
Participants will receive subcutaneous (SC) natalizumab 300 mg every 4 weeks for 60 weeks.
Drug: BG00002 (Natalizumab) SC
Natalizumab for Subcutaneous Injection
Other Names:
  • Tysabri
  • BG00002
Experimental: Natalizumab 300 mg IV every 12 weeks
Participants will receive intravenous natalizumab 300 mg every 12 weeks for 60 weeks. Matching IV placebo will be administered during the intervening 4 week periods.
Drug: BG00002 (Natalizumab) IV
Natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Drug: IV Placebo
Intravenous placebo to natalizumab
Experimental: Natalizumab 300 mg SC every 12 weeks
Participants will receive subcutaneous natalizumab 300 mg every 12 weeks for 60 weeks. Matching SC placebo will be administered during the intervening 4 week periods.
Drug: BG00002 (Natalizumab) SC
Natalizumab for Subcutaneous Injection
Other Names:
  • Tysabri
  • BG00002
Drug: SC Placebo
Subcutaneous placebo to natalizumab
Experimental: Natalizumab 150 mg IV every 12 weeks
Participants will receive intravenous natalizumab 150 mg every 12 weeks for 60 weeks. Matching IV placebo will be administered during the intervening 4 week periods.
Drug: BG00002 (Natalizumab) IV
Natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Drug: IV Placebo
Intravenous placebo to natalizumab
Experimental: Natalizumab 150 mg SC every 12 weeks
Participants will receive subcutaneous natalizumab 150 mg every 12 weeks for 60 weeks. Matching SC placebo will be administered during the intervening 4 week periods.
Drug: BG00002 (Natalizumab) SC
Natalizumab for Subcutaneous Injection
Other Names:
  • Tysabri
  • BG00002
Drug: SC Placebo
Subcutaneous placebo to natalizumab

Detailed Description:

This is a blinded, prospective, randomized, dose-ranging study in patients with RRMS who have received natalizumab for at least 12 months according to the local prescribing guidelines. The study will explore dosing of natalizumab by subcutaneous and intravenous routes. Participants will be randomly assigned to 1 of 6 dosing regimens, blinded to natalizumab dose, but not route, for 60 weeks of treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Ability to provide written informed consent
  • Subjects of childbearing potential must practice effective contraception during the study
  • A documented diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS)
  • Free of MS relapse for 12 months prior to randomization
  • Treatment with natalizumab for a minimum of 12 months immediately prior to randomization.
  • In the 12 months prior to commencing natalizumab, subject must have experienced a minimal level of disease activity as defined by 2 or more documented clinical relapses OR 1 relapse and documented MRI activity, defined by the presence of at least 1 Gd enhancing lesion on MRI, unrelated to the relapse.

Key Exclusion Criteria:

  • Known history of Human Immunodeficiency Virus (HIV), hepatitis C and/or hepatitis B virus
  • Positive for anti-natalizumab antibodies at screening
  • MRI positive for Gd-enhancing lesions at study entry
  • Subjects for whom MRI is contraindicated
  • History of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease
  • History of malignant disease, including solid tumors and hematologic malignancies (with the exception of cured basal cell and squamous cell carcinomas of the skin)
  • History of transplantation or any anti-rejection therapy
  • History of severe allergic or anaphylactic reactions or known hypersensitivity to any drug
  • A clinically significant infectious illness within 30 days prior to screening or progressive multifocal leukoencephalopathy (PML) or other opportunistic infections at any time
  • Signs or symptoms suggestive of any serious infection, based on medical history, physical examination or laboratory testing

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: NCT01405820

  Show 64 Study Locations
Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT01405820     History of Changes
Other Study ID Numbers: 101MS206, 2010-024000-10
Study First Received: July 14, 2011
Last Updated: June 26, 2014
Health Authority: Italy: Ethics Committee
France: Institutional Ethical Committee
Spain: Comité Ético de Investigación Clínica
Belgium: Institutional Review Board
Germany: Ethics Commission

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 28, 2014