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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

Primary Purpose

Cystic Fibrosis

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

ivacaftor

Placebo

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

3 Years - 5 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part 1-Sequence 1

Part 1 - Sequence 2

Part 2: ivacaftor

Arm Description

ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2

placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2

open label period

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Absolute Change From Baseline in Weight at Week 8

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).

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Full Information

NCT ID

NCT02742519

First Posted

April 14, 2016

Last Updated

October 20, 2018

Sponsor

Vertex Pharmaceuticals Incorporated

1. Study Identification

Unique Protocol Identification Number

NCT02742519

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Terminated

Why Stopped

Low enrollment.

Study Start Date

May 2016 (undefined)

Primary Completion Date

August 2017 (Actual)

Study Completion Date

August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1-Sequence 1

Arm Type

Experimental

Arm Description

ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2

Arm Title

Part 1 - Sequence 2

Arm Type

Experimental

Arm Description

placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2

Arm Title

Part 2: ivacaftor

Arm Type

Experimental

Arm Description

open label period

Intervention Type

Drug

Intervention Name(s)

ivacaftor

Other Intervention Name(s)

VX-770

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Absolute Change From Baseline in Lung Clearance Index (LCI2.5) Through 8 Weeks of Treatment (Average of Week 4 and Week 8 LCI2.5)

Description

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Time Frame

Baseline Through Week 8 for each treatment period, Up to 24 Weeks

Secondary Outcome Measure Information:

Title

Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8

Description

Serum samples were collected for evaluation of change in immunoreactive trypsinogen levels at Week 8.

Time Frame

Baseline and Week 8 of each treatment period, Up to 24 Weeks

Title

Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8

Description

Fecal elastase-1 was used clinically to diagnose pancreatic exocrine insufficiency in participants with cystic fibrosis.

Time Frame

Baseline and Week 8 of each treatment period, Up to 24 Weeks

Title

Absolute Change From Baseline in Weight at Week 8

Time Frame

Baseline and Week 8 of each treatment period, Up to 24 Weeks

Title

Absolute Change From Baseline in Body Mass Index (BMI) at Week 8

Description

BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

Time Frame

Baseline and Week 8 of each treatment period, Up to 24 Weeks

Title

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame

Baseline up to Month 15

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

City

Parkville

State/Province

Victoria

Country

Australia

City

South Brisbane

Country

Australia

City

Subiaco

Country

Australia

City

Westmead

Country

Australia

City

Toronto

State/Province

Ontario

Country

Canada

City

London

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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