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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):

Study Description
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).

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

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : August 2011
Primary Completion Date : April 2014
Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.
Drug: natalizumab IV
natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
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.
Drug: natalizumab IV
natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Drug: natalizumab SC
natalizumab for Subcutaneous Injection
Other Names:
  • Tysabri
  • BG00002
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.
Drug: 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
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.
Drug: natalizumab IV
natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Drug: 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
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.
Drug: 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
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.
Drug: natalizumab IV
natalizumab for IV Infusion
Other Names:
  • Tysabri
  • BG00002
Drug: natalizumab SC
natalizumab for Subcutaneous Injection
Other Names:
  • Tysabri
  • BG00002
Drug: SC Placebo
Subcutaneous placebo to natalizumab


Outcome Measures

Primary Outcome Measures :
  1. 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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01405820


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

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01405820     History of Changes
Other Study ID Numbers: 101MS206
2010-024000-10 ( EudraCT Number )
First Posted: July 29, 2011    Key Record Dates
Results First Posted: July 29, 2015
Last Update Posted: August 21, 2015
Last Verified: August 2015

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