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

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01405820
• Other study ID #: 101MS206
• Secondary ID: 2010-024000-10
• Status: Completed
• Phase: Phase 2
• First received: July 14, 2011
• Last updated: August 3, 2015
• Start date: August 2011
• Est. completion date: October 2014

Study information

• Verified date: August 2015
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeFrance: Institutional Ethical CommitteeSpain: Comité Ético de Investigación ClínicaBelgium: Institutional Review BoardGermany: Ethics Commission
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: October 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• natalizumab IV
natalizumab for IV Infusion
• natalizumab SC
natalizumab for Subcutaneous Injection
• IV Placebo
Intravenous placebo to natalizumab
• SC Placebo
Subcutaneous placebo to natalizumab

Locations

Country	Name	City	State
Belgium	Research Site	Brasschaat
Belgium	Research Site	Liege
Belgium	Research Site	Overpelt
Belgium	Research Site	Wilrijk
France	Research Site	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
Germany	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
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
Italy	Research Site	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
Spain	Research Site	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

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No