Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS)
REFINE
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
2 other identifiers
interventional
290
5 countries
64
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2011
Typical duration for phase_2
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 14, 2011
CompletedFirst Posted
Study publicly available on registry
July 29, 2011
CompletedStudy Start
First participant enrolled
August 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2014
CompletedResults Posted
Study results publicly available
July 29, 2015
CompletedAugust 21, 2015
August 1, 2015
2.7 years
July 14, 2011
June 29, 2015
August 3, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Cumulative Number of Combined Unique Active Lesions
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.
Up to Week 60
Study Arms (6)
Natalizumab 300 mg Intravenous (IV) Every 4 Weeks
ACTIVE COMPARATORNatalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks
EXPERIMENTALNatalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Natalizumab 300 mg IV Every 12 Weeks
EXPERIMENTALNatalizumab 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.
Natalizumab 300 mg SC Every 12 Weeks
EXPERIMENTALNatalizumab 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.
Natalizumab 150 mg IV Every 12 Weeks
EXPERIMENTALNatalizumab 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.
Natalizumab 150 mg SC Every 12 Weeks
EXPERIMENTALNatalizumab 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
natalizumab for IV Infusion
natalizumab for Subcutaneous Injection
Intravenous placebo to natalizumab
Subcutaneous placebo to natalizumab
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (64)
Research Site
Brasschaat, Belgium
Research Site
Liège, Belgium
Research Site
Overpelt, Belgium
Research Site
Wilrijk, Belgium
Research Site
Amiens, France
Research Site
Besançon, France
Research Site
Bron, France
Research Site
Lille, France
Research Site
Montpellier, France
Research Site
Nantes, France
Research Site
Nice, France
Research Site
Paris, France
Research Site
Rennes, France
Research Site
Strasbourg, France
Research Site
Toulouse, France
Research Site
Andernach, Germany
Research Site
Bamberg, Germany
Research Site
Berlin, Germany
Research Site
Bochum, Germany
Research Site
Bonn, Germany
Research Site
Dresden, Germany
Research Site
Emmendingen, Germany
Research Site
Erbach im Odenwald, Germany
Research Site
Erlangen, Germany
Research Site
Frankfurt, Germany
Research Site
Freiburg im Breisgau, Germany
Research Site
Heidelberg, Germany
Research Site
Jena, Germany
Research Site
Mainz, Germany
Research Site
Marburg, Germany
Research Site
München, Germany
Research Site
Neuburg am Inn, Germany
Research Site
Regensburg, Germany
Research Site
Tübingen, Germany
Research Site
Ulm, Germany
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Wermsdorf, Germany
Research Site
Bari, Italy
Research Site
Catania, Italy
Research Site
Cefalù, Italy
Research Site
Chieti, Italy
Research Site
Florence, Italy
Research Site
Gallarate, Italy
Research Site
L’Aquila, Italy
Research Site
Milan, Italy
Research Site
Montichiari, Italy
Research Site
Napoli, Italy
Research Site
Orbassano, Italy
Research Site
Padua, Italy
Research Site
Palermo, Italy
Research Site
Pavia, Italy
Research Site
Pozzilli, Italy
Research Site
Roma, Italy
Research Site
Sassari, Italy
Research Site
Torino, Italy
Research Site
Barcelona, Spain
Research Site
Donostia / San Sebastian, Spain
Research Site
Girona, Spain
Research Site
Lleida, Spain
Research Site
Málaga, Spain
Research Site
Murcia, Spain
Research Site
Oviedo, Spain
Research Site
Pamplona, Spain
Research Site
Santa Cruz de Tenerife, Spain
Research Site
Seville, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Biogen Study Medical Director
- Organization
- Biogen
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 14, 2011
First Posted
July 29, 2011
Study Start
August 1, 2011
Primary Completion
April 1, 2014
Study Completion
October 1, 2014
Last Updated
August 21, 2015
Results First Posted
July 29, 2015
Record last verified: 2015-08