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

A Phase 3b, 2-part, Randomized, Double-blind, Placebo-controlled Crossover Study With a Long-term Open-label Period to Investigate Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation

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

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: ivacaftor

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia
  • Subiaco, Australia
  • Westmead, Australia
  • Victoria
    • Parkville, Victoria, Australia
• Canada
  • Ontario
    • Toronto, Ontario, Canada
• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1-Sequence 1; ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2	Drug: Placebo; Drug: ivacaftor; Other Names: VX-770
Experimental: Part 1 - Sequence 2; placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2	Drug: Placebo; Drug: ivacaftor; Other Names: VX-770
Experimental: Part 2: ivacaftor; open label period	Drug: ivacaftor; Other Names: VX-770

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8	Serum samples were collected for evaluation of change in immunoreactive trypsinogen levels at Week 8.	Baseline and Week 8 of each treatment period, Up to 24 Weeks
Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8	Fecal elastase-1 was used clinically to diagnose pancreatic exocrine insufficiency in participants with cystic fibrosis.	Baseline and Week 8 of each treatment period, Up to 24 Weeks
Absolute Change From Baseline in Weight at Week 8		Baseline and Week 8 of each treatment period, Up to 24 Weeks
Absolute Change From Baseline in Body Mass Index (BMI) at Week 8	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).	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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 14, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): November 19, 2018
• Last Update Submitted That Met QC Criteria: October 20, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX15-770-123; 2015-001267-39 (EudraCT Number)