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

Purpose

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.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Ivacaftor Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Ivacaftor

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:

Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
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 [ Time Frame: Day 0 to 15, Day 16 to 56, Day 57 to 112, Day 113 to 168 ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline up to follow-up (3 to 4 weeks after last dose [last dose = Week 24]) ] [ Designated as safety issue: Yes ]
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.


Enrollment:	70
Study Start Date:	July 2012
Study Completion Date:	October 2013
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Ivacaftor Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks.	Drug: Ivacaftor Ivacaftor 150 milligram (mg) tablet orally twice daily for 24 weeks. Other Names: Kalydeco VX-770
Placebo Comparator: Placebo Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.	Drug: Placebo Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks.

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.

Eligibility


Ages Eligible for Study:	6 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01614457

Show 31 Study Locations

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Cystic Fibrosis Foundation Therapeutics

Investigators


Principal Investigator:	Richard Moss, MD	Stanford University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT01614457 History of Changes
Other Study ID Numbers:	VX11-770-110
Study First Received:	June 5, 2012
Results First Received:	January 31, 2015
Last Updated:	January 31, 2015
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:


Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases	Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 23, 2016

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