Abstract
OBJECTIVE: To evaluate the safety and pharmacokinetics/pharmacodynamics of AMY109, an anti-interleukin-8 recycling antibody in a first-in-human phase 1 trial in healthy volunteers (HVs) and patients with endometriosis. DESIGN: A multicenter, randomized, double-blind, placebo-controlled single-dose and multiple ascending-dose study in Japan and Taiwan. SUBJECTS: Asian and White HVs in part 1 and patients with endometriosis aged ≥20 to <50 years in part 2. INTERVENTION: In part 1, sequential cohorts of HVs randomly received a single subcutaneous dose of AMY109 (0.6, 2.0, 3.5, or 5.0 mg/kg) or placebo. In part 2, sequential cohorts of patients with endometriosis randomly received a once-monthly subcutaneous dose of AMY109 (0.8, 2.0, or 5.0 mg/kg) or placebo for 6 months. MAIN OUTCOME MEASURES: The primary objective was to assess the safety and tolerability of AMY109. Pharmacokinetic profiles and efficacy were evaluated as secondary and exploratory endpoints, respectively. RESULTS: Overall, 42.1% (32/76) of HVs in part 1 and 61.5% (16/26) of patients in part 2 experienced at least one adverse event during the study. The most common adverse events were oropharyngeal pain, pharyngitis, upper respiratory tract infections, and upper respiratory tract inflammation in part 1 (≥5.0%) and vomiting, nasopharyngitis, diarrhea, nausea, and vaccination site pain in part 2 (≥15.0%). Most events were mild to moderate in severity and were resolved/resolving at last follow-up. Of note, menstrual bleeding in patients with endometriosis was not interrupted during AMY109 treatment. Pharmacokinetic analysis showed that AMY109 had a long half-life (40 days) and exhibited linear pharmacokinetics across all cohorts. CONCLUSION: AMY109 demonstrated acceptable safety and pharmacokinetic profiles in HVs (single dose of 0.6-5.0 mg/kg) and patients with endometriosis (multiple doses of 0.8-5.0 mg/kg/month for 6 months). These results support further clinical development of AMY109 for endometriosis and other diseases influenced by interleukin-8. TRIAL REGISTRATION NUMBER: AMY001JG study; JapicCTI-183841. Trial registration date: January 25, 2018. Date of first participant's enrolment: February 26, 2018.