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

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ClinicalTrials.gov Identifier: NCT01405820
Recruitment Status : Completed
First Posted : July 29, 2011
Results First Posted : July 29, 2015
Last Update Posted : August 21, 2015
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE July 14, 2011
First Posted Date  ICMJE July 29, 2011
Results First Submitted Date  ICMJE June 29, 2015
Results First Posted Date  ICMJE July 29, 2015
Last Update Posted Date August 21, 2015
Study Start Date  ICMJE August 2011
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2015)
Cumulative Number of Combined Unique Active Lesions [ Time Frame: Up to Week 60 ]
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 Up to Week 60.
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
The cumulative number of new active lesions compared to baseline brain MRI scans at week 60 [ Time Frame: Baseline to week 60 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2011)
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 72 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS)
Official Title  ICMJE 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
Brief Summary 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).
Detailed Description This is a a dose and frequency (but not route of administration) 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Relapsing-Remitting Multiple Sclerosis
Intervention  ICMJE
  • Drug: natalizumab IV
    natalizumab for IV Infusion
    Other Names:
    • Tysabri
    • BG00002
  • Drug: natalizumab SC
    natalizumab for Subcutaneous Injection
    Other Names:
    • Tysabri
    • BG00002
  • Drug: IV Placebo
    Intravenous placebo to natalizumab
  • Drug: SC Placebo
    Subcutaneous placebo to natalizumab
Study Arms  ICMJE
  • Active Comparator: Natalizumab 300 mg Intravenous (IV) Every 4 Weeks
    Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Intervention: Drug: natalizumab IV
  • Experimental: Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks
    Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Interventions:
    • Drug: natalizumab IV
    • Drug: natalizumab SC
  • Experimental: Natalizumab 300 mg IV Every 12 Weeks
    Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Interventions:
    • Drug: natalizumab IV
    • Drug: IV Placebo
  • Experimental: Natalizumab 300 mg SC Every 12 Weeks
    Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Interventions:
    • Drug: natalizumab IV
    • Drug: natalizumab SC
    • Drug: SC Placebo
  • Experimental: Natalizumab 150 mg IV Every 12 Weeks
    Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Interventions:
    • Drug: natalizumab IV
    • Drug: IV Placebo
  • Experimental: Natalizumab 150 mg SC Every 12 Weeks
    Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
    Interventions:
    • Drug: natalizumab IV
    • Drug: natalizumab SC
    • Drug: SC Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 29, 2015)
290
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2011)
300
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01405820
Other Study ID Numbers  ICMJE 101MS206
2010-024000-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Biogen
Original Responsible Party Biogen Idec Medical Director
Current Study Sponsor  ICMJE Biogen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP