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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)

Primary Purpose

Relapsing-Remitting Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
natalizumab IV
natalizumab SC
IV Placebo
SC Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Natalizumab 300 mg Intravenous (IV) Every 4 Weeks

Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks

Natalizumab 300 mg IV Every 12 Weeks

Natalizumab 300 mg SC Every 12 Weeks

Natalizumab 150 mg IV Every 12 Weeks

Natalizumab 150 mg SC Every 12 Weeks

Arm Description

Natalizumab 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 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 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 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 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 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
July 14, 2011
Last Updated
August 3, 2015
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT01405820
Brief Title
Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS)
Acronym
REFINE
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 Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
290 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Natalizumab 300 mg Intravenous (IV) Every 4 Weeks
Arm Type
Active Comparator
Arm Description
Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Arm Title
Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks
Arm Type
Experimental
Arm Description
Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.
Arm Title
Natalizumab 300 mg IV Every 12 Weeks
Arm Type
Experimental
Arm Description
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.
Arm Title
Natalizumab 300 mg SC Every 12 Weeks
Arm Type
Experimental
Arm Description
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.
Arm Title
Natalizumab 150 mg IV Every 12 Weeks
Arm Type
Experimental
Arm Description
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.
Arm Title
Natalizumab 150 mg SC Every 12 Weeks
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
natalizumab IV
Other Intervention Name(s)
Tysabri, BG00002
Intervention Description
natalizumab for IV Infusion
Intervention Type
Drug
Intervention Name(s)
natalizumab SC
Other Intervention Name(s)
Tysabri, BG00002
Intervention Description
natalizumab for Subcutaneous Injection
Intervention Type
Drug
Intervention Name(s)
IV Placebo
Intervention Description
Intravenous placebo to natalizumab
Intervention Type
Drug
Intervention Name(s)
SC Placebo
Intervention Description
Subcutaneous placebo to natalizumab
Primary Outcome Measure Information:
Title
Cumulative Number of Combined Unique Active Lesions
Description
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.
Time Frame
Up to Week 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Brasschaat
Country
Belgium
Facility Name
Research Site
City
Liege
Country
Belgium
Facility Name
Research Site
City
Overpelt
Country
Belgium
Facility Name
Research Site
City
Wilrijk
Country
Belgium
Facility Name
Research Site
City
Amiens cedex 1
Country
France
Facility Name
Research Site
City
Besançon Cedex
Country
France
Facility Name
Research Site
City
Bron cedex
Country
France
Facility Name
Research Site
City
Lille Cedex
Country
France
Facility Name
Research Site
City
Montpellier
Country
France
Facility Name
Research Site
City
Nantes Cedex 01
Country
France
Facility Name
Research Site
City
Nice cedex
Country
France
Facility Name
Research Site
City
Paris Cedex
Country
France
Facility Name
Research Site
City
Rennes Cedex 9
Country
France
Facility Name
Research Site
City
Strasbourg
Country
France
Facility Name
Research Site
City
Toulouse cedex 9
Country
France
Facility Name
Research Site
City
Andernach
Country
Germany
Facility Name
Research Site
City
Bamberg
Country
Germany
Facility Name
Research Site
City
Berlin
Country
Germany
Facility Name
Research Site
City
Bochum
Country
Germany
Facility Name
Research Site
City
Bonn
Country
Germany
Facility Name
Research Site
City
Dresden
Country
Germany
Facility Name
Research Site
City
Emmendingen
Country
Germany
Facility Name
Research Site
City
Erbach
Country
Germany
Facility Name
Research Site
City
Erlangen
Country
Germany
Facility Name
Research Site
City
Frankfurt
Country
Germany
Facility Name
Research Site
City
Freiburg
Country
Germany
Facility Name
Research Site
City
Heidelberg
Country
Germany
Facility Name
Research Site
City
Jena
Country
Germany
Facility Name
Research Site
City
Mainz
Country
Germany
Facility Name
Research Site
City
Marburg
Country
Germany
Facility Name
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City
München
Country
Germany
Facility Name
Research Site
City
Neuburg
Country
Germany
Facility Name
Research Site
City
Regensburg
Country
Germany
Facility Name
Research Site
City
Tuebingen
Country
Germany
Facility Name
Research Site
City
Ulm
Country
Germany
Facility Name
Research Site
City
Wermsdorf
Country
Germany
Facility Name
Research Site
City
Bari
Country
Italy
Facility Name
Research Site
City
Catania
Country
Italy
Facility Name
Research Site
City
Cefalù
Country
Italy
Facility Name
Research Site
City
Chieti
Country
Italy
Facility Name
Research Site
City
Firenze
Country
Italy
Facility Name
Research Site
City
Gallarate
Country
Italy
Facility Name
Research Site
City
L'Aquila
Country
Italy
Facility Name
Research Site
City
Milano
Country
Italy
Facility Name
Research Site
City
Montichiari
Country
Italy
Facility Name
Research Site
City
Napoli
Country
Italy
Facility Name
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City
Orbassano
Country
Italy
Facility Name
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City
Padova
Country
Italy
Facility Name
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City
Palermo
Country
Italy
Facility Name
Research Site
City
Pavia
Country
Italy
Facility Name
Research Site
City
Pozzilli
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
Sassari
Country
Italy
Facility Name
Research Site
City
Torino
Country
Italy
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Girona
Country
Spain
Facility Name
Research Site
City
Lleida
Country
Spain
Facility Name
Research Site
City
Malaga
Country
Spain
Facility Name
Research Site
City
Murcia
Country
Spain
Facility Name
Research Site
City
Oviedo
Country
Spain
Facility Name
Research Site
City
Pamplona
Country
Spain
Facility Name
Research Site
City
San Sebastian
Country
Spain
Facility Name
Research Site
City
Santa Cruz de Tenerife
Country
Spain
Facility Name
Research Site
City
Sevilla
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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