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

Biogen

Status and phase: Completed; Phase 2

Conditions: Relapsing-Remitting Multiple Sclerosis

Treatments: Drug: natalizumab IV; Drug: IV Placebo; Drug: SC Placebo; Drug: natalizumab SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01405820

101MS206

2010-024000-10 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 290 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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290 participants in 6 patient groups

Natalizumab 300 mg Intravenous (IV) Every 4 Weeks

Active Comparator group

Description:

Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Treatment:

Drug: natalizumab IV

Natalizumab 300 mg Subcutaneous (SC) Every 4 Weeks

Experimental group

Description:

Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Treatment:

Drug: natalizumab SC

Drug: natalizumab IV

Natalizumab 300 mg IV Every 12 Weeks

Experimental group

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.

Treatment:

Drug: IV Placebo

Drug: natalizumab IV

Natalizumab 300 mg SC Every 12 Weeks

Experimental group

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.

Treatment:

Drug: SC Placebo

Drug: natalizumab SC

Drug: natalizumab IV

Natalizumab 150 mg IV Every 12 Weeks

Experimental group

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.

Treatment:

Drug: IV Placebo

Drug: natalizumab IV

Natalizumab 150 mg SC Every 12 Weeks

Experimental group

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.

Treatment:

Drug: SC Placebo

Drug: natalizumab SC

Drug: natalizumab IV