To assess ocrelizumab efficacy on upper limb function in more disabled/older patients with primary progressive multiple sclerosis (PPMS) from the Phase III ORATORIO study (NCT01194570) to inform the design of the Phase IIIb ORATORIO-HAND study.

Ocrelizumab demonstrated efficacy versus placebo in reducing upper limb dysfunction (9-Hole Peg Test [9HPT]) in ORATORIO (Expanded Disability Status Scale [EDSS] ≤6.5). Ocrelizumab benefit in more disabled PPMS patients ineligible for inclusion in ORATORIO would fulfill an unmet need.

ORATORIO PPMS patients (N=732; EDSS 3.0–6.5; age 18–55 years) were randomized (2:1) to ocrelizumab or placebo for ≥120 weeks and until a pre-specified number of EDSS progression events occurred. Efficacy of ocrelizumab in preventing progression of upper limb function as measured by 12-week confirmed 20% worsening in 9HPT (average of both hands) was investigated in baseline subgroups: EDSS ≥6.0 (N=220), age >45 years (N=384), and 9HPT time >25 seconds (N=434).

Ocrelizumab reduced upper limb disability progression in more disabled/older PPMS patients. Risk reductions versus placebo in 9HPT progression were similar in patients with baseline EDSS score <6.0 and ≥6.0 (40% versus 38%, p=0.92), and baseline 9HPT time ≤25s and >25s (49% versus 44%, p=0.82). Progression events mainly occurred in patients with 9HPT >25s versus ≤25s (placebo: 34.3% vs 17.8%; ocrelizumab: 21.5% vs 9.9%); a weak trend for greater efficacy in patients ≤45 years versus >45 years was observed (p=0.29).

ORATORIO-HAND is designed to further investigate the efficacy of ocrelizumab on upper limb function. Based on the 9HPT progression rates observed in ORATORIO, 1000 eligible patients (EDSS 3.0-8.0, age 18–65 years, 9HPT >25s), randomized (1:1) to ocrelizumab or placebo for ≥120 weeks (until a pre-specified number of progression events occur) will enable the assessment of ocrelizumab efficacy on confirmed 9HPT progression (primary endpoint). Screening will begin Q1 2019.