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

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).

Study Overview

• Status: Completed
• Conditions: Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: natalizumab IV; Drug: natalizumab SC; Drug: IV Placebo; Drug: SC Placebo

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: Interventional
• Enrollment (Actual): 290
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brasschaat, Belgium
    • Research Site
  • Liege, Belgium
    • Research Site
  • Overpelt, Belgium
    • Research Site
  • Wilrijk, Belgium
    • Research Site
• France
  • Amiens cedex 1, France
    • Research Site
  • Besançon Cedex, France
    • Research Site
  • Bron cedex, France
    • Research Site
  • Lille Cedex, France
    • Research Site
  • Montpellier, France
    • Research Site
  • Nantes Cedex 01, France
    • Research Site
  • Nice cedex, France
    • Research Site
  • Paris Cedex, France
    • Research Site
  • Rennes Cedex 9, France
    • Research Site
  • Strasbourg, France
    • Research Site
  • Toulouse cedex 9, France
    • Research Site
• Germany
  • 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, Germany
    • Research Site
  • Erlangen, Germany
    • Research Site
  • Frankfurt, Germany
    • Research Site
  • Freiburg, Germany
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  • Heidelberg, Germany
    • Research Site
  • Jena, Germany
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  • Mainz, Germany
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  • Marburg, Germany
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  • München, Germany
    • Research Site
  • Neuburg, Germany
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  • Regensburg, Germany
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  • Tuebingen, Germany
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  • Ulm, Germany
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  • Wermsdorf, Germany
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• Italy
  • Bari, Italy
    • Research Site
  • Catania, Italy
    • Research Site
  • Cefalù, Italy
    • Research Site
  • Chieti, Italy
    • Research Site
  • Firenze, Italy
    • Research Site
  • Gallarate, Italy
    • Research Site
  • L'Aquila, Italy
    • Research Site
  • Milano, Italy
    • Research Site
  • Montichiari, Italy
    • Research Site
  • Napoli, Italy
    • Research Site
  • Orbassano, Italy
    • Research Site
  • Padova, 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
• Spain
  • Barcelona, Spain
    • Research Site
  • Girona, Spain
    • Research Site
  • Lleida, Spain
    • Research Site
  • Malaga, Spain
    • Research Site
  • Murcia, Spain
    • Research Site
  • Oviedo, Spain
    • Research Site
  • Pamplona, Spain
    • Research Site
  • San Sebastian, Spain
    • Research Site
  • Santa Cruz de Tenerife, Spain
    • Research Site
  • Sevilla, Spain
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 14, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Estimate): August 21, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: 101MS206; 2010-024000-10 (EudraCT Number)