A Phase II, Randomized, Double Blind, Placebo Controlled Study of Safety, Pharmacokinetics, and Biomarker Results of Subcutaneous Bapineuzumab in Patients with mild to moderate Alzheimer's disease.
BACKGROUND Bapineuzumab, a humanized monoclonal antibody, targets amyloid b (Ab1 40/1 42) that is believed to play a key role in the pathogenesis of Alzheimer disease (AD) OBJECTIVES To assess the effects of monthly subcutaneous (SC) bapineuzumab versus placebo on cerebral amyloid signal in amyloid positive patients with mild to moderate AD. The incidence of amyloid related imaging abnormalities edema/effusion (ARIA E) pharmacokinetics, pharmacodynamics, immunogenicity, and other safety aspects of bapineuzumab were also evaluated. METHODS In this multicenter, double blind study, 146 patients were randomized (1 1:1 1) to SC bapineuzumab 2, 7, or 20 mg/month or placebo. Lack of efficacy of intravenous (IV) bapineuzumab in Phase III studies led to truncation of the treatment duration from 24 months to 12 months. Primary endpoint: change from baseline to month 12 in brain amyloid signal as measured by standardized uptake value ratio (SUVR) using florbetapir positron emission tomography (PET) RESULTS Florbetapir PET SUVR decreased significantly (p 0.038) from baseline to month 12 for the bapineuzumab 7 mg/month group only; reductions versus placebo were not significant for any dosage. One patient each in bapineuzumab 2 mg/month and 20 mg/month groups had ARIA E. The percentages of patients with treatment emergent adverse events were similar in placebo (77.8% and bapineuzumab 2 mg/month (78.4% group, but higher in 7 mg/month (94.4% and 20 mg/month (89.2% groups. CONCLUSION Bapineuzumab SC once monthly did not demonstrate significant treatment difference over placebo on cerebral amyloid signal at one year but was well tolerated. There was less ARIA E than had been expected based on prior experience with comparable exposure on IV bapineuzumab.
Journal of Alzheimer's disease JAD