A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)
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| ClinicalTrials.gov Identifier: NCT02637856 |
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Recruitment Status :
Completed
First Posted : December 22, 2015
Results First Posted : May 26, 2020
Last Update Posted : May 26, 2020
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Sponsor:
Genentech, Inc.
Information provided by (Responsible Party):
Genentech, Inc.
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Brief Summary:
This study will evaluate the efficacy and safety of ocrelizumab in participants with RRMS who have had a suboptimal response to an adequate course of DMT. Participants will receive ocrelizumab as an initial dose of two 300-milligrams (mg) intravenous (IV) infusions (600 mg total) separated by 14 days followed by one 600-mg IV infusion for a maximum of 4 doses (up to 96 weeks). Anticipated time on study treatment is 96 weeks.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Sclerosis, Relapsing-Remitting | Drug: Ocrelizumab | Phase 3 |
Participants who complete their Week 72 ocrelizumab infusion and do not experience any serious infusion related reaction (IRR) throughout the main study will be eligible to enroll in an optional, open-label, non-randomized substudy to MN30035 and receive one additional shorter infusion of ocrelizumab at the Week 96 visit. This substudy will enroll approximately 100 patients from MN30035 main study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 608 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Relapsing Remitting Multiple Sclerosis Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment |
| Actual Study Start Date : | February 11, 2016 |
| Actual Primary Completion Date : | May 3, 2019 |
| Actual Study Completion Date : | May 3, 2019 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple sclerosis
MedlinePlus related topics:
Multiple Sclerosis
Drug Information available for:
Ocrelizumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ocrelizumab
Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).
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Drug: Ocrelizumab
Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).
Other Name: RO4964913 |
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Experimental: Ocrelizumab (substudy)
Participants with no serious IRR throughout the main study will be eligible to enroll in an optional substudy and receive one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab will be administered IV as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
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Drug: Ocrelizumab
Participants will receive an additional single 600-mg dose IV infusion at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)
Other Name: RO4964913 |
Primary Outcome Measures :
- Percentage of Participants Without Any Protocol-Defined Events During 96-Week Period [ Time Frame: Baseline up to Week 96 ]Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 gadolinium (Gd)-enhanced lesion on brain magnetic resonance imaging (MRI) or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.
- Percentage of Participants With Infusion Related Reactions (IRRs) in Optional Substudy [ Time Frame: Week 96 to Week 100 ]Rate and frequency of Grade 3 or 4 IRRs with onset on or after the shorter ocrelizumab infusion
Secondary Outcome Measures :
- Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period [ Time Frame: Baseline up to Weeks 24 and 48 ]Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.
- Time to Protocol-Defined Event [ Time Frame: Baseline up to Week 96 ]Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.
- Total Number of Protocol-Defined Relapses Per Participant Year During 96-week Period [ Time Frame: Baseline up to Week 96 ]Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for greater than (>) 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days. The Adjusted Annualized Relapse Rate was adjusted by baseline Expanded Disability Status Scale (EDSS <2.5 vs. >=2.5) and number of previous disease-modifying treatments (DMTs =1 vs. >1)
- Time to Onset of First Protocol-Defined Relapse [ Time Frame: Baseline up to Week 96 ]Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for >24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days.
- Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI [ Time Frame: Baseline up to Week 96 ]
- Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI [ Time Frame: Baseline up to Week 96 ]
- Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks According to Expanded Disability Status Scale (EDSS) Score [ Time Frame: Baseline up to Week 96 ]
- Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI [ Time Frame: Weeks 24, 48, and 96 ]The analyses included participants who had an interpretable MRI at the time point of interest. Participants having 0, 1, 2, 3, and greater than 3 lesions at weeks 24, 48, and 96 were included in the analysis.
- Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 24, 48, and 96 ]Baseline data is represented as mean; post-Baseline date are represented as mean changes.
- Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI [ Time Frame: Weeks 24, 48, and 96 ]
- Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 100 weeks ]An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
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| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of multiple sclerosis (specifically RRMS), in accordance with the revised 2010 McDonald criteria
- Disease duration from first symptom of less than or equal to (</=) 12 years
- Treated with an adequate course of treatment with no more than three prior DMT regimens of greater than or equal to (>/=) 6 months, and the discontinuation of the most recent adequately used DMT was due to suboptimal response
- Suboptimal response while the participant was on his/her last adequately used DMT for >/=6 months (defined by having one of the following qualifying events despite being on a stable dose of the same DMT for at least 6 months: one or more clinically reported relapses, one or more T1 Gd-enhanced lesions, or two or more new or enlarging T2 lesions on MRI); these qualifying events must have occurred while on the last adequately used DMT. In participants receiving stable doses of the same approved DMT for more than a year, the event must have occurred within the last 12 months of treatment with this DMT from the date of screening
Exclusion Criteria:
- History of primary progressive multiple sclerosis (PPMS), progressive relapsing multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)
- Contraindications for MRI
- Known presence of other neurological disorders that may mimic multiple sclerosis
- Pregnancy or lactation, or intention to become pregnant during the study
- Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- History of or currently active primary or secondary immunodeficiency
- Lack of peripheral venous access
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Active infection, or history of or known presence of recurrent or chronic infection such as human immunodeficiency virus (HIV), syphilis, or tuberculosis
- History of progressive multifocal leukoencephalopathy
- Contraindications to or intolerance of oral or IV corticosteroids
- Previous treatment with fingolimod (Gilenya®) or dimethyl fumarate (Tecfidera®) in participants whose lymphocyte count is below the lower limit of normal (LLN)
- Treatment with alemtuzumab (Lemtrada®)
- Previous treatment with systemic cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, or methotrexate
- Previous treatment with natalizumab within 12 months prior to screening unless failure was due to confirmed, persistent anti-drug antibodies (ADAs). Participants previously treated with natalizumab will be eligible for this study only if duration of treatment with natalizumab was less than (<) 1 year and natalizumab was not used in the 12 months prior to screening. Anti-John Cunningham virus (JCV) antibody status (positive or negative) and titer (both assessed within the year of screening) must be documented prior to enrollment
- Treatment with dalfampridine (Ampyra®) unless on stable dose for >/=30 days prior to screening
- Treatment with a B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
- Treatment with a drug that is experimental (Exception: treatment with an experimental drug that was subsequently approved in the participant's country is allowed)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02637856
Locations
Show 82 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Study Documents (Full-Text)
Documents provided by Genentech, Inc.:
Documents provided by Genentech, Inc.:
Study Protocol [PDF] June 19, 2018
Statistical Analysis Plan [PDF] April 30, 2019
| Responsible Party: | Genentech, Inc. |
| ClinicalTrials.gov Identifier: | NCT02637856 |
| Other Study ID Numbers: |
MN30035 |
| First Posted: | December 22, 2015 Key Record Dates |
| Results First Posted: | May 26, 2020 |
| Last Update Posted: | May 26, 2020 |
| Last Verified: | May 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases |
Demyelinating Diseases Autoimmune Diseases Immune System Diseases Ocrelizumab Immunologic Factors Physiological Effects of Drugs |