A Study to Evaluate Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation

Phase 3

Terminated

• Conditions: Cystic Fibrosis
• Interventions: Drug: ivacaftor; Drug: Placebo

• Registration Number: NCT02742519
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

To evaluate the efficacy of ivacaftor treatment, as measured by lung clearance index (LCI), in subjects with cystic fibrosis (CF) who have a specified CF transmembrane conductance regulator (CFTR) gating mutation

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-14
• Study First Submitted QC: 2016-04-14
• Study First Posted: 2016-04-19
• Study Start: 2016-05
• Primary Completion: 2017-08
• Study Completion: 2017-08
• Results First Submitted: 2018-08-31
• Status Verified: 2018-10
• Results First Submitted QC: 2018-10-20
• Last Update Submitted: 2018-10-20
• Results First Posted: 2018-11-19
• Last Update Posted: 2018-11-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Male or female with confirmed diagnosis of CF.
• Must have 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.
• Hematology, serum chemistry, and coagulation at Screening with no clinically significant abnormalities or concomitant diagnosis that would interfere with the LCI and CT scan study assessments, as judged by the investigator.

Exclusion Criteria

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
• Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator)
• Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin
• History of solid organ or hematological transplantation
• Any clinically significant "non-CF-related" illness within 2 weeks before Day 1
• Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
• Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before Screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1-Sequence 1	Placebo	ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2
Part 1 - Sequence 2	Placebo	placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2
Part 1-Sequence 1	ivacaftor	ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2
Part 1 - Sequence 2	ivacaftor	placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2
Part 2: ivacaftor	ivacaftor	open label period

Primary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Lung Clearance Index (LCI2.5) Through 8 Weeks of Treatment (Average of Week 4 and Week 8 LCI2.5)	Baseline Through Week 8 for each treatment period, Up to 24 Weeks	LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8	Baseline and Week 8 of each treatment period, Up to 24 Weeks	Fecal elastase-1 was used clinically to diagnose pancreatic exocrine insufficiency in participants with cystic fibrosis.
Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8	Baseline and Week 8 of each treatment period, Up to 24 Weeks	Serum samples were collected for evaluation of change in immunoreactive trypsinogen levels at Week 8.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 8	Baseline and Week 8 of each treatment period, Up to 24 Weeks	BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Absolute Change From Baseline in Weight at Week 8	Baseline and Week 8 of each treatment period, Up to 24 Weeks
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to Month 15