Efficacy and Safety of Nanoencapsulated Sirolimus plus Pegadricase: Results from the Randomized, Placebo-Controlled Phase 3 Trials.

Abstract

DISSOLVE I and II examined efficacy and safety of nanoencapsulated sirolimus (NAS) plus pegadricase (NASP) in patients with uncontrolled gout (UG). In these double-blind, placebo-controlled Phase 3 trials of NASP, patients were randomized 1:1:1 to infusions of high-dose (HD) or low-dose (LD) NAS plus pegadricase (HD NASP, LD NASP, respectively) or placebo, given every 4 weeks for 6 doses. The primary endpoint was proportion of patients with serum urate (SU) <6 mg/dL for ≥80% of the time during Weeks 21-24. Secondary endpoints included health-related quality of life, tophus resolution, tender joints, and gout flares. Safety was also assessed. Overall, 265 patients received HD NASP, LD NASP, or placebo. SU response during Weeks 21-24 was significantly higher with NASP than placebo (HD NASP: 51%; LD NASP: 43%; placebo: 8%; p<0.0001 for both doses vs placebo). Common adverse events included gout flares (HD NASP: 42.5%; LD NASP: 44.3%; placebo: 43.3%), infections (HD NASP: 23.0%; LD NASP: 18.2%; placebo: 16.7%), and stomatitis (HD NASP: 9.2%; LD NASP: 3.4%; placebo: 0%). Infusion reactions within 1 hour were infrequent (4%) in NASP-treated patients. During Weeks 1-12, the proportion of patients with flares was similar between NASP- and placebo-treated patients; thereafter, it decreased in NASP-treated patients but remained unchanged with placebo. NASP treatment resulted in a significantly higher proportion of patients with complete SU response during Weeks 21-24 compared to placebo and was generally well-tolerated. NASP, an every-4-week treatment, can markedly alleviate disease burden in patients with UG.