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

August 3, 2015 updated by: Biogen

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
290

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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
        • Research Site
      • Heidelberg, Germany
        • Research Site
      • Jena, Germany
        • Research Site
      • Mainz, Germany
        • Research Site
      • Marburg, Germany
        • Research Site
      • München, Germany
        • Research Site
      • Neuburg, Germany
        • Research Site
      • Regensburg, Germany
        • Research Site
      • Tuebingen, Germany
        • Research Site
      • Ulm, Germany
        • Research Site
      • Wermsdorf, Germany
        • Research Site
  • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Up to Week 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 21, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 101MS206
  • 2010-024000-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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