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Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-{alpha}, in subjects with rheumatoid arthritis: A randomised, double-blind, placebo-controlled, phase I, first-in-human study
Annals of Rheumatic Diseases, 06/10/2011
Clinical Article
Burmester GR et al. – In this first-in-human study, mavrilimumab showed preliminary evidence of pharmacodynamic activity. The safety and pharmacokinetic profiles of mavrilimumab support further clinical studies in RA.
Methods- Randomised, double-blind, placebo-controlled, dose-escalating phase I study
- Subjects with RA who received stable methotrexate treatment for ≥3 months before enrolment
- Subjects received single intravenous escalating doses of mavrilimumab (0.01–10.0 mg/kg) or placebo
- 32 subjects were enrolled in this study (1 unblinded subject at 0.01 mg/kg and another at 0.03 mg/kg followed by 5 sequential double-blinded cohorts, n=6 each, treated with 0.1, 0.3, 1.0, 3.0 and 10.0 mg/kg)
- AEs mild or moderate and reported with similar frequency across all treatment cohorts
- One subject (10.0 mg/kg) experienced moderate face and neck urticaria during infusion that resolved with symptomatic treatment
- Systemic clearance of mavrilimumab approached that of endogenous IgG at doses >1.0 mg/kg; pharmacodynamic activity confirmed in 1.0 and 3.0 mg/kg cohorts by suppression of suppressor of cytokine signalling 3 mRNA transcripts
- In exploratory analyses, reductions of acute phase reactants observed in subjects with elevated CRP (>5 mg/l) and ESR (≥20.0 mm/h) at baseline
- No significant change in Disease Activity Score 28-joint assessment (DAS28) seen in any of cohorts
- In mavrilimumab-treated subjects (n=15) with baseline DAS28 >3.2, mean disease activity (DAS28) significantly reduced at 4 weeks
