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

Study Overview
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Brief Summary
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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).

Official Title
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Phase II, Multicenter, Randomized, Parallel-Group, Partially Blinded, Placebo and Avonex Controlled Dose Finding Study to Evaluate the Efficacy As Measured by Brain MRI Lesions, and Safety of 2 Dose Regimens of Ocrelizumab in Patients With RRMS

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Placebo
* Drug: Ocrelizumab
* Drug: Avonex


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Placebo matching to ocrelizumab administered as IV infision in Cycle 1 Day 1.<br>|
| Experimental: Ocrelizumab 600 mg<br>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. | Drug: Ocrelizumab<br>* Ocrelizumab 300 mg was administered in cycle 1 followed by an infusion of ocrelizumab 600 mg on Day 1. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4.<br>* Other names: RO4964913;|
| Experimental: Ocrelizumab 1000 mg<br>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. | Drug: Ocrelizumab<br>* Ocrelizumab 300 mg was administered in cycle 1 followed by an infusion of ocrelizumab 600 mg on Day 1. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4.<br>* Other names: RO4964913;|
| Active Comparator: Avonex<br>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. | Drug: Avonex<br>* Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1.<br>* Other names: Interferon-beta-alpha1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain | Mean of total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 12, 16, 20, 24 was determined using average imputation method. | Week 12 to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Protocol Defined Relapse Rate at Week 24 | Adjusted annualized relapse rate for geographical region. | Week 24 | 
| Percentage of Participants Who Remained Relapse Free at Week 24 | Percentage of participants who remained relapse free at week 24 were reported. | Week 24 | 
| Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24 | Change from baseline in total volume of T2 lesions on MRI scans of the Brain at week 24 was reported. | Baseline, Week 24 | 
| Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain | Total number of new gadolinium-enhancing T1 lesions observed by MRI scans of the brain were reported. | Weeks 4 to Week 24 | 
| Total Number of Gadolinium-Enhancing T1 Lesions at Weeks | Total number of gadolinium-enhancing T1 lesions at weeks were reported. | Weeks 4 to Week 24 |