The aim of the study was to assess dose-response effects of the anti-CD20 monoclonal antibody Ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis ( RMS ).
Patients ( n = 232 ) were randomized to Ofatumumab 3, 30, or 60 mg every 12 weeks, Ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new Gadolinium-enhancing lesions ( per brain MRI ) at week 12.
Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured.
Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion.
The cumulative number of new lesions was reduced by 65% for all Ofatumumab dose groups vs placebo ( p less than 0.001 ).
Post hoc analysis ( excluding weeks 1-4 ) estimated a greater than or equal to 90% lesion reduction vs placebo ( week 12 ) for all cumulative Ofatumumab doses greater than or equal to 30 mg/12 week.
Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect.
The most common adverse event was injection-related reactions ( 52% Ofatumumab, 15% placebo ), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing.
In conclusion, imaging showed that all subcutaneous Ofatumumab doses demonstrated efficacy ( most robust: cumulative doses greater than or equal to 30 mg/12 week ), with a safety profile consistent with existing Ofatumumab data.
This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells. ( Xagena )
Bar-Or A et al, Neurology 2018;90(20):e1805-e1814