Table 1.
Pivotal MS Trials with Ocrelizumab
| Study | Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis1 | Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis2 |
|---|---|---|
| Design | Phase 3, randomized 2:1 OCR vs placebo | Tandem (2) phase 3 trials, randomized 1:1 OCR vs IFNβ-1a |
| Number of Patients | 732 (488 OCR; 244 placebo) | 821 (410 OCR; 411 IFNβ-1a) + 835 (417 OCR; 418 IFNβ-1a) |
| Key Inclusion Criteria | Age: 18–55; EDSS: 3.0–6.5; Motor FSS: 2+; Disease duration: <10yrs if EDSS 3–5, <15yrs if EDSS 5–6.5; Elevated IgG index or 1+ OCB; No prior B cell depletion or immune suppression | Age: 18–55; RMS; EDSS: 1–5.5 (unless EDSS <2 after 10yrs); No prior anti-CD20, ALEM; No recent IFN, GA, IVIg, PLEX; 2 or more relapses/2yrs or 1 relapse in past yr |
| Dose | All doses: OCR 600mg q24wks; each given as paired 300mg IV infusions 2wks apart; 100mg methylprednisolone IV before each infusion. | OCR 600mg q24wks (initial course given as paired 300mg IV infusions 2wks apart; 100mg methylprednisolone IV before each infusion) vs IFNβ-1a 44μg tiw |
| Duration | Event-driven; approx.120wks (2.3yrs) | 96wks (1.8yrs) |
| Primary Outcome | % pts with CDP-12 (24% reduction favoring OCR) | ARR (46% and 47% reductions favoring OCR) |
| Significant Secondary Outcomes | Clinical: CDP-24, T25W; MRI: T2 lesion volume, whole brain volume loss | Clinical: CDP-12, CDP-24, CDI-12, MSFC (pooled analyses); MRI: Gd+ lesions, new-enlarging lesions |
| Adverse Events | Infusion reactions; Minor URIs; Oral herpes infections (nonserious); Imbalance in breast cancer, possibly other neoplasms, of uncertain significance | Infusion reactions |
| Comments | First effective disease-modifying therapy for PPMS. FDA approval for dosing identical to RMS (single 600mg dose q24wks after initial paired 300mg infusions). | Highly effective against relapses and new MRI lesions; significant benefits against disability. |
Montalban, X, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209–220
Hauser, SL, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221–234 ALEM = alemtuzumab; ARR = annualized relapse rate; CDI-12 = 12-week confirmed disability improvement; CDP-12 = 12-week confirmed disability progression; CDP-24 = 24-week confirmed disability progression; EDSS = expanded disability status scale; FDA = Food & Drug Administration; FSS = functional systems score; GA = glatiramer acetate; Gd+ = gadolinium-enhancing; IFN = interferon; IFNβ-1a = interferon beta-1a; IgG = immunoglobulin G; IV = intravenous; IVIg = intravenous immunoglobulin; mg = milligram; MRI = magnetic resonance imaging; MSFC = multiple sclerosis functional composite; OCB = oligoclonal band; OCR = ocrelizumab; PLEX = plasma exchange; PPMS = primary progressive multiple sclerosis; pts = patients; RMS = relapsing multiple sclerosis; T25W = timed 25-foot walk; tiw = three times weekly; URI = upper respiratory tract infection; wks = weeks; yrs = years; μg = microgram