Study of the Effect of Ivacaftor on Lung Clearance Index in Subjects With Cystic Fibrosis and the G551D Mutation

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of VX-770 on Lung Clearance Index in Subjects With Cystic Fibrosis, the G551D Mutation, and FEV1 >90% Predicted

The purpose of this study is to evaluate the effect of ivacaftor (VX-770) on lung clearance index (LCI) in subjects aged 6 years and older with cystic fibrosis (CF) who have the G551D-CFTR mutation on at least 1 allele.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ivacaftor; Drug: Placebo

Detailed Description

Currently, limited objective measures are available to quantify lung function in CF patients with mild lung disease. Lung clearance index (LCI) derived from inert gas multiple-breath washout (MBW) testing hold considerable promise to evaluate early lung disease as studies have detected abnormalities in a high percentage of CF patients with normal spirometry in both infants and children.

This study explored the effect of ivacaftor on LCI and the efficacy of ivacaftor on other clinical and biomarker endpoints of CF lung disease in subjects aged 6 years and older with CF who have the G551D-CFTR mutation on at least 1 allele.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
• United Kingdom
  • Belfast, United Kingdom
  • Edinburgh, United Kingdom
  • London, United Kingdom
• United States
  • California
    • Stanford, California, United States
  • Iowa
    • Iowa City, Iowa, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects with confirmed diagnosis of CF
• Must have the G551D-CFTR mutation in at least 1 allele
• FEV1 >90% of predicted normal for age, gender, and height

Exclusion Criteria:

• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
• Use of inhaled hypertonic saline treatment within 2 weeks of the Period 1, Day 1 visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.	Drug: Ivacaftor; 150 mg tablet, oral use, twice daily every 12 hours (q12h); Drug: Placebo; Tablet, oral use, twice daily every 12 hours (q12h)
Experimental: Treatment Sequence 2; Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2.	Drug: Ivacaftor; 150 mg tablet, oral use, twice daily every 12 hours (q12h); Drug: Placebo; Tablet, oral use, twice daily every 12 hours (q12h)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Lung Clearance Index (LCI)	Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal SF6 concentration to 1/40th of the starting value.	Baseline through Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Percent Predicted FEV1	Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.	Baseline through Day 29
Change From Baseline in Sweat Chloride	The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.	Baseline through Day 29
Change From Baseline in CF Questionnaire-Revised (CFQ-R) Score (Respiratory Domain Score, Pooled)	The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). The primary analytical focus was the respiratory health domain, which was analyzed by combining all self-response questionnaire versions from different age groups (e.g., Adult/Adolescent and Child versions).	Baseline through Day 29

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jane Davies, Royal Brompton Hospital and Imperial College; Principal Investigator: Felix Ratjen, The Hospital for Sick Children

Publications and helpful links

General Publications

• Davies J, Sheridan H, Bell N, Cunningham S, Davis SD, Elborn JS, Milla CE, Starner TD, Weiner DJ, Lee PS, Ratjen F. Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Lancet Respir Med. 2013 Oct;1(8):630-638. doi: 10.1016/S2213-2600(13)70182-6. Epub 2013 Sep 10. Erratum In: Lancet Respir Med. 2017 Jul;5(7):e26.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 4, 2013
• Last Verified: February 1, 2013

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: VX10-770-106