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Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT) (KONDUCT)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ivacaftor
Placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female with confirmed diagnosis of CF
  • Must have at least 1 allele of the R117H CFTR mutation
  • Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) predicted normal for age, sex, and height
  • 6 years of age or older
  • Minimum weight of 15 kilogram (kg) at screening
  • Females of childbearing potential must not be pregnant
  • Willing to comply with contraception requirements

Exclusion Criteria:

  • CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D)
  • History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
  • Abnormal liver function, at screening, defined as greater than or equal to (>=) 3 time 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), total bilirubin
  • Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening
  • History of solid organ or hematological transplantation
  • History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
  • Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis)
  • Use of any inhibitors or inducers of cytochrome (CYP) P450 3A

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ivacaftor

Placebo

Arm Description

Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.

Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.

Outcomes

Primary Outcome Measures

Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years.

Secondary Outcome Measures

Change From Baseline in Body Mass Index (BMI) at Week 24
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Change From Baseline in Sweat Chloride Through Week 24
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life
Time to First Pulmonary Exacerbation
Number of events (pulmonary exacerbation) during the pre-specified time intervals were reported. A subject without an exacerbation before withdrawal from the study was considered censored at the time of withdrawal, and a subject without an exacerbation who completes the study period was considered censored at the end of the analysis period.
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence, including clinically significant clinical laboratory assessments which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.

Full Information

First Posted
June 5, 2012
Last Updated
January 31, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01614457
Brief Title
Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)
Acronym
KONDUCT
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
Cystic Fibrosis Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have the R117H-CFTR mutation.
Detailed Description
Ivacaftor is the first CFTR modulator to show an improvement in CFTR function and clinical benefit in subjects with CF. Results from Phase 3 studies (VX08-770-102 [Study 102] [NCT00909532] and VX08-770-103 [Study 103] [NCT00909727]) showed that ivacaftor is effective in the treatment of subjects with CF who have the G551D-CFTR mutation, as evidenced by sustained improvements in CFTR channel function (measured by reduction in sweat chloride concentration) and corresponding substantial, durable improvements in lung function, pulmonary exacerbations, respiratory symptoms, and weight gain. Ivacaftor was also well tolerated, as evidenced by the rates and reasons for premature discontinuation and results of safety assessments. Ivacaftor (Trade Name Kalydeco; 150 mg tablets) was initially approved in the United States for the treatment of CF in subjects 6 years of age and older who have a G551D mutation in the CFTR gene.

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
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ivacaftor
Arm Type
Experimental
Arm Description
Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
Kalydeco, VX-770
Intervention Description
Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years.
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Body Mass Index (BMI) at Week 24
Description
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Time Frame
Baseline, Week 24
Title
Change From Baseline in Sweat Chloride Through Week 24
Description
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24
Description
The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life
Time Frame
Baseline, Week 24
Title
Time to First Pulmonary Exacerbation
Description
Number of events (pulmonary exacerbation) during the pre-specified time intervals were reported. A subject without an exacerbation before withdrawal from the study was considered censored at the time of withdrawal, and a subject without an exacerbation who completes the study period was considered censored at the end of the analysis period.
Time Frame
Day 0 to 15, Day 16 to 56, Day 57 to 112, Day 113 to 168
Title
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
AE: any untoward medical occurrence, including clinically significant clinical laboratory assessments which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Time Frame
Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24])

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female with confirmed diagnosis of CF Must have at least 1 allele of the R117H CFTR mutation Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) predicted normal for age, sex, and height 6 years of age or older Minimum weight of 15 kilogram (kg) at screening Females of childbearing potential must not be pregnant Willing to comply with contraception requirements Exclusion Criteria: CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D) History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug Abnormal liver function, at screening, defined as greater than or equal to (>=) 3 time 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), total bilirubin Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening History of solid organ or hematological transplantation History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis) Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Moss, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
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Birmingham
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Belfast
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Edinburgh
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12. IPD Sharing Statement

Citations:
PubMed Identifier
26070913
Citation
Moss RB, Flume PA, Elborn JS, Cooke J, Rowe SM, McColley SA, Rubenstein RC, Higgins M; VX11-770-110 (KONDUCT) Study Group. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med. 2015 Jul;3(7):524-33. doi: 10.1016/S2213-2600(15)00201-5. Epub 2015 Jun 9.
Results Reference
derived

Learn more about this trial

Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have the R117H-CF Transmembrane Conductance Regulator (CFTR) Mutation (KONDUCT)

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