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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01405820
First received: July 14, 2011
Last updated: August 3, 2015
Last verified: August 2015

July 14, 2011
August 3, 2015
August 2011
April 2014   (final data collection date for primary outcome measure)
Cumulative Number of Combined Unique Active Lesions [ Time Frame: Up to Week 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 Up to Week 60.
The cumulative number of new active lesions compared to baseline brain MRI scans at week 60 [ Time Frame: Baseline to week 60 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01405820 on ClinicalTrials.gov Archive Site
Not Provided
The number of participants with adverse events [ Time Frame: Participants will be followed for the duration of the study; an expected 72 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS)
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

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Relapsing-Remitting Multiple Sclerosis
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
290
October 2014
April 2014   (final data collection date for primary outcome measure)

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.

Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   France,   Germany,   Italy,   Spain
 
NCT01405820
101MS206, 2010-024000-10
Yes
Biogen
Biogen
Not Provided
Study Director: Medical Director Biogen
Biogen
August 2015

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