A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis

Genentech

Status and phase: Completed; Phase 2

Conditions: Multiple Sclerosis, Relapsing-Remitting

Treatments: Drug: Ocrelizumab; Drug: Avonex; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00676715

ACT4422g

2007-006338-32 (EudraCT Number)

WA21493 (Other Identifier)

Details and patient eligibility

About

This is a phase II, multicenter, randomized, parallel-group, partially blinded, placebo and Avonex (interferon beta-1a) controlled dose finding study to evaluate the efficacy as measured by brain MRI lesions, and safety of 2 dose regimens of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS).

Enrollment: 220 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
• Relapsing-remitting multiple sclerosis (MS)
• Ages 18-55 years inclusive
• For sexually active female and male participants of reproductive potential, use of reliable means of contraception

Exclusion criteria

• Secondary or primary progressive multiple sclerosis at screening
• Incompatibility with MRI
• Contra-indications to or intolerance of oral or IV corticosteroids
• Known presence of other neurologic disorders
• Pregnancy or lactation
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal
• Congestive heart failure
• Known active bacterial, viral, fungal, mycobacterial infection or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
• History or known presence of recurrent or chronic infection
• History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix of the uterus that have been excised and resolved)
• History of alcohol or drug abuse within 24 weeks prior to randomization
• History of or currently active primary or secondary immunodeficiency
• History of coagulation disorders
• Treatment with any investigational agent within 4 weeks of screening
• Receipt of a live vaccine within 6 weeks prior to randomization
• Incompatibility with Avonex use
• Previous treatment with rituximab
• Previous treatment with lymphocyte-depleting therapies except mitoxantrone
• Treatment with lymphocyte trafficking blockers within 24 weeks prior to randomization
• Treatment with beta interferons, glatiramer acetate, IV immunoglobulin, plasmapheresis, or immunosuppressive therapies within 12 weeks prior to randomization
• Systemic corticosteroid therapy within 4 weeks prior to randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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220 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received two intravenous (IV) infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days.

Treatment:

Drug: Placebo

Ocrelizumab 600 mg

Experimental group

Description:

Participants two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.

Treatment:

Drug: Ocrelizumab

Ocrelizumab 1000 mg

Experimental group

Description:

Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days.

Treatment:

Drug: Ocrelizumab

Avonex

Active Comparator group

Description:

Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of OCR 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.

Treatment:

Drug: Avonex