Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial
In this double-blind, phase 2 trial, 324 patients with relapsing multiple sclerosis were randomly assigned to receive weekly subcutaneous injections with atacicept (25, 75, or 150 mg) or placebo. Atacicept is a humanised recombinant protein that binds to some cytokines which are involved in B-cell differentiation, maturation, and survival.
Patients underwent standardised neurological examination, at screening, on study day 1, and then every 12 weeks to week 48. MRI was done at screening, on study day 1, week 12, and then every four weeks to week 36. The primary endpoint was the change in mean number of gadolinium-enhancing lesions on T1-weighted MRI per patient per scan between weeks 12 and 36. Safety endpoints were: the nature, severity, and frequency of adverse events; infections; laboratory abnormalities; injection-site reactions; changes in vital signs; changes in electrocardiography findings; and the proportion of patients with antibodies to atacicept.
The study was terminated early after the independent data and safety monitoring board noted an increased annualised relapse rate with atacicept.
Mature B-cell counts fell in all atacicept groups compared with placebo and atacicept was associated with a dose-dependent reduction in serum immunoglobulin concentrations as well. The overall frequency and severity of adverse events and serious adverse events were similar across the treatment groups in the safety population during both the double-blind period and the safety follow-up of ATAMS. Injection-site reaction was the most frequently reported treatment-emergent adverse event.
Authors: Kappos L, Hartung HP.
Source: Lancet Neurol. 2014 Apr;13(4):353-63. doi: 10.1016/S1474-4422(14)70028-6. Epub 2014 Mar 6.
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