A Phase III, Open-label Study to Evaluate the Effect of Ocrelizumab on Immune Responses in Patients With Relapsing Multiple Sclerosis
Objectives: To characterize humoral immune responses to vaccines in patients with relapsing MS treated with OCR.
Methods: Patients will be randomized (2:1) to receive OCR 600mg as two 300mg intravenous infusions on Day 1 and Day 15; Group A will receive OCR prior to immunization and Group B will remain treatment-naive/continue with interferon treatment during immunization. Group B patients will be immunized with tetanus toxoid (TT)–containing adsorbed vaccine on Day 1, 23-valent pneumococcal polysaccharide vaccine (23-PPV) on Day 28, keyhole limpet hemocyanin (KLH) on Days 1, 28, and 56, and influenza vaccine during Weeks 1-12. Group A patients will be immunized ≥12 weeks after first OCR administration: TT at Week 12, 23-PPV at Week 16, and KLH at Weeks 12, 16, and 20. Group A patients will be further divided to either receive booster 13-pneumococcal conjugate vaccine (13-PCV; Group A1) or influenza vaccine (Group A2). All groups will undergo post-immunization assessments until the end of the study period (Group A: Day 169/Week 24; Group B: Day 84/Week 12). Key eligibility criteria include at least 1 previous immunization against TT, tetanus or diphtheria; or tetanus, diphtheria and acellular pertussis.
Results: The primary outcome measure will compare positive TT responses (IgG) 8 weeks post-immunization in patients in Groups A1 and A2 vs Group B. Key secondary outcomes include: proportions of patients in Groups A1 and A2 vs. Group B with a positive response against individual anti-pneumococcal antibody serotype at 4 weeks post–23-PPV; mean levels of anti-KLH antibody (IgG) in Group A vs. Group B at 4 weeks post–last KLH administration; proportion of patients in Group A1 vs. Group B with positive responses against an individual anti-pneumococcal antibody serotype at 4 weeks post–booster 13-PCV administration; proportion of patients in Group A2 vs. Group B who achieve seroprotection at 4 weeks post–influenza vaccine administration; measures of B- and T-cell subsets and natural killer cells; and overall safety.
Conclusions: This study will evaluate whether patients undergoing treatment with OCR can effectively mount protective immune responses against clinically relevant vaccines and will further determine immunization recommendations.
Supported by F. Hoffmann-La Roche Ltd.