A phase 3, 2-part, single-arm study of ivacaftor treatment in patients <2 years with a CFTR gating mutation: Results from the ARRIVAL study in patients 1 to 2 years

Abstract

Objectives: Ivacaftor (IVA) is a safe effective therapy for children with CF aged ≥2 yrs (y). Analyses of 1- to < 2-y-olds completing the ARRIVAL study (ongoing for pts <1 y) are presented. Methods: Pts received IVA (50 mg if 7 to <14 kg, 75 mg if ≥14 kg) q12 h for 5 days in Part A (A) and 50 mg q12 h for 24 wks in Part B (B). Primary endpoints were safety (A, B) and PK (A). Secondary/Exploratory endpoints (B) included PK, change in sweat chloride (SwCl), growth/nutrition, fecal elastase-1 (FE-1), serum immunoreactive trypsinogen (IRT), lipase, and amylase. Results: Parts A and B enrolled 7 and 19 pts (mean age, 19.1 and 15.2 mo), respectively. The most common AE was cough (A, 43%; B, 74%). Most AEs were mild/moderate. Two pts had SAEs, both in Part B (PEx, DIOS, constipation, eczema herpeticum). Two pts (11%) had increased ALT >8 × ULN but resumed IVA after interruption; both had concurrent infections. No pts discontinued due to AEs. Substantial improvement was seen in SwCl and FE-1, a marker of pancreatic exocrine function (Table). Asymptomatic elevations of serum IRT, lipase, and amylase noted at baseline (BL) decreased with IVA. Mean nutritional status was normal at BL and maintained during treatment. Conclusion: These data suggest that IVAwas safe andwell tolerated in pts 1 to 2 y. Substantial improvements were seen in SwCl, indicating improved CFTR function. Rapid reduction in raised BL amylase and lipase with IVA is a new observation, and along with improvements in FE-1 and IRT, support a window in early life for improving pancreatic function. Sponsored by Vertex Pharmaceuticals Incorporated. (Table Presented).L6229306912018-07-12 <br />