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

• Sponsor: Genentech, Inc.
• Collaborator: Roche Pharma AG
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: May 9, 2008
• First Posted Date: May 13, 2008
• Results First Submitted Date: March 31, 2017
• Results First Posted Date: May 11, 2017
• Last Update Posted Date: March 19, 2019
• Actual Study Start Date: July 31, 2008
• Actual Primary Completion Date: March 9, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2017)

Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain [ Time Frame: Week 12 to Week 24 ]

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.

• Original Primary Outcome Measures (submitted: May 9, 2008): Total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain [ Time Frame: Weeks 12, 16, 20 and 24 ]
• Change History: Complete list of historical versions of study NCT00676715 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 31, 2017)

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

Original Secondary Outcome Measures (submitted: May 9, 2008)

• The annualized protocol defined relapse rate [ Time Frame: Week 24 ]
• Proportion of patients who remain relapse-free [ Time Frame: Week 24 ]
• Change in total volume of T2 lesions on MRI scans of the brain [ Time Frame: Baseline to week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis
• Official Title: 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
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Multiple Sclerosis, Relapsing-Remitting

Intervention

• Drug: Placebo
  Placebo matching to ocrelizumab administered as IV infision in Cycle 1 Day 1.
• Drug: Ocrelizumab
  Two infusion 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.
  Other Name: RO4964913
• Drug: Ocrelizumab
  Ocrelizumab 1000 mg IV infusions was administered on cycle 1 Day 1.
  Other Name: RO4964913
• Drug: Ocrelizumab
  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.
  Other Name: RO4964913
• Drug: Avonex
  Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1.
  Other Name: Interferon-beta-alpha1

Study Arms

• Placebo Comparator: Placebo
  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.
  Interventions:

  • Drug: Placebo
  • Drug: Ocrelizumab
• Experimental: Ocrelizumab 600 mg
  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.
  Intervention: Drug: Ocrelizumab
• Experimental: Ocrelizumab 1000 mg
  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.
  Intervention: Drug: Ocrelizumab
• Active Comparator: Avonex
  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.
  Interventions:

  • Drug: Ocrelizumab
  • Drug: Avonex

• Publications *: Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011 Nov 19;378(9805):1779-87. doi: 10.1016/S0140-6736(11)61649-8. Epub 2011 Oct 31.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 31, 2017): 220
• Original Estimated Enrollment (submitted: May 9, 2008): 250
• Estimated Study Completion Date: December 9, 2021
• Actual Primary Completion Date: March 9, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Canada, Czechia, Denmark, Finland, France, Germany, Italy, Mexico, Netherlands, Romania, Russian Federation, Serbia, Slovakia, Spain, Switzerland, Ukraine, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00676715
• Other Study ID Numbers: ACT4422g; 2007-006338-32 ( EudraCT Number ); WA21493 ( Other Identifier: Hoffmann-La Roche )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Genentech, Inc.
• Study Sponsor: Genentech, Inc.
• Collaborators: Roche Pharma AG

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: March 2019