Phase 3
N=821
A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis
Relapsing Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT01247324 ↗Enrolled (actual)
821
Serious AEs
19.1%
Results posted
Jul 2017
Primary outcome: Primary: Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks — 0.292; 0.156 relapses/participant year of treatment — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Interferon beta-1a (Drug); Ocrelizumab-matching placebo (Drug); Ocrelizumab (Drug); Interferon beta-1a-matching placebo (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks |
0.292; 0.156 | <0.0001 sig |
| SECONDARY Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period |
NA; NA | = 0.0139 sig |
| SECONDARY Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment |
337; 21 | < 0.0001 sig |
| SECONDARY Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment |
1916; 430 | < 0.0001 sig |
| SECONDARY Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks |
12.42; 20.00 | = 0.0106 sig |
| SECONDARY Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period |
NA; NA | = 0.0278 sig |
| SECONDARY Number of T1 Hypointense Lesions During the Double-Blind Treatment |
1307; 564 | < 0.0001 sig |
| SECONDARY Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 |
0.028; -0.012; 0.174; 0.213 | = 0.3261 |
| SECONDARY Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 |
-0.741; -0.572 | = 0.0042 sig |
| SECONDARY Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 |
45.399; 45.065; -0.657; 0.036 | = 0.2193 |
| SECONDARY Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 |
27.1; 47.4 | < 0.0001 sig |
| SECONDARY Number of Participants With Adverse Events (AEs) |
331; 327; 302; 319 | — |
| SECONDARY Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) |
3513 | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab |
2; 1; 2; 1 | — |
Summary
This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Planned duration of double-blind treatment is 96 weeks. Participants who complete the 96-week double-blind treatment will have an option to enter a single-group, active-treatment, open-label extension period, providing they fulfill the eligibility criteria.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
- At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
- Neurologic stability for greater than or equal to (>=) 30 days prior to both screening and baseline
- Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive
Exclusion Criteria
- Primary progressive multiple sclerosis
- Disease duration of more than 10 years in participants with EDSS less than or equal to (<=) 2.0 at screening
- Contraindications for MRI
- Known presence of other neurological disorders which may mimic multiple sclerosis
- Pregnancy or lactation
- Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
- History of or currently active primary or secondary immunodeficiency
- 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 (e.g., hepatitis B or C, human immunodeficiency virus [HIV], syphilis, tuberculosis)
- History of progressive multifocal leukoencephalopathy
- Contraindications to or intolerance of oral or iv corticosteroids
- Contraindications to Rebif or incompatibility with Rebif use
Data sourced from ClinicalTrials.gov (NCT01247324). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.