Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial

摘要: Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate regulation blood-brain barrier's permeability. Masitinib, selective oral tyrosine kinase inhibitor, effectively inhibits survival, migration activity mast cells. As brain rich cells, therapeutic potential masitinib as an adjunct therapy standard care was investigated. A randomised, placebo-controlled, phase 2 study performed patients with mild-to-moderate disease, receiving cholinesterase inhibitor and/or memantine. Patients were randomly assigned receive (n = 26) (starting dose 3 or 6 mg/kg/day) placebo 8), administered twice daily for 24 weeks. The primary endpoint change from baseline Disease Assessment Scale - cognitive subscale (ADAS-Cog) assess function related patient response rate. rate clinically relevant decline according ADAS-Cog (increase >4 points) after 12 weeks significantly lower adjunctive treatment compared (6% vs. 50% both time points; P 0.040 0.046, respectively). Moreover, whilst arm showed worsening mean ADAS-Cog, Cooperative Study Activities Daily Living Inventory, Mini-Mental State Examination scores, reported improvements, statistical significance between arms at week (respectively, 0.016 0.030; 0.035 0.128; 0.047 0.031). effect score relative 6.8 7.6, respectively. Adverse events occurred more frequently (65% 38% patients); however, majority mild moderate intensity transitory. Severe adverse similar frequency (15% 13% patients, Masitinib-associated included gastrointestinal disorders, oedema, rash. Masitinib add-on during associated slower acceptable tolerance profile. may therefore represent innovative avenue disease. This trial provides evidence that support larger placebo-controlled investigation. Clinicaltrials.gov NCT00976118