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S112 Long-term safety and efficacy of ivacaftor in paediatric patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation
  1. JC Davies1,
  2. S Robertson2,
  3. J Cooke3,
  4. M Higgins3,
  5. M Rosenfeld4
  1. 1Imperial College London and Royal Brompton and Harefield NHS Foundation Trust, London, UK
  2. 2Vertex Pharmaceuticals Incorporated, Boston, MA, USA
  3. 3Vertex Pharmaceuticals (Europe) Limited, London, UK
  4. 4Seattle Children’s Hospital, Seattle, WA, USA

Abstract

Background and objectives The 24-week open-label Phase 3 KIWI study demonstrated that the pharmacokinetics and safety of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation are similar to those seen in older patients.¹ We report the final results from KLIMB, the long-term open-label extension of KIWI.

Methods Patients who completed KIWI Part B enrolled in KLIMB and received ivacaftor for an additional 84 weeks. Patients aged 2–5 years received weight-based dosing (50 mg q12h for weight < 14 kg; 75 mg q12 h for ≥14 kg); patients who turned 6 received 150 mg q12h. The primary endpoint was safety. Secondary endpoints included change from baseline (at the start of KIWI) in sweat chloride, weight, and body mass index (BMI). Exploratory endpoints included faecal elastase-1 (FE-1) and immunoreactive trypsinogen (IRT) levels.

Results Of 34 patients in KIWI Part B, 33 enrolled in KLIMB (mean age at KLIMB baseline, 3.7 years). Five patients discontinued study drug (1 for elevated alanine transaminase/aspartate transaminase [ALT/AST] levels, 2 switched to commercial ivacaftor, 2 for noncompliance). The most common adverse event (AE) of any grade was cough (73%). Eleven patients had serious AEs; 2 were considered related to ivacaftor (elevated ALT/AST levels). Ten patients had elevated ALT/AST levels > 3 × upper limit of normal (ULN). Of these, 4 had elevated ALT/AST levels > 8 × ULN in KIWI; ivacaftor was maintained or resumed in all patients except 1 who discontinued. Significant improvements in sweat chloride, FE-1 and IRT levels, and BMI z scores were observed at week 84 (Table 1).

Conclusion Ivacaftor demonstrated a stable safety profile during an extended 84-week follow-up period in patients with cystic fibrosis aged 2–5 years with a CFTR gating mutation. Reported AEs were consistent with the known safety profile; the incidence of elevated ALT/AST levels per 24-week period was consistent with that observed in KIWI. The improvements seen in KIWI in sweat chloride, BMI z score, and measures of pancreatic function were maintained at the end of KLIMB.

Sponsored by Vertex Pharmaceuticals Incorporated

Please refer to page A270 for declarations of interest in relation to abstract S112.

Abstract S112 Table 1

Absolute Change From KIWI Baseline

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