Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation (KONNECTION)

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01614470
First received: June 5, 2012
Last updated: October 23, 2014
Last verified: October 2014

June 5, 2012
October 23, 2014
July 2012
October 2013   (final data collection date for primary outcome measure)
  • Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8 [ Time Frame: Part 1: Baseline (pre-dose Day 1), Week 8 ] [ 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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
  • Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit) [ Time Frame: Baseline (pre-dose Week 12), Week 36 ] [ 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. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) [ Time Frame: Through 8 weeks and 24 weeks of treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01614470 on ClinicalTrials.gov Archive Site
  • Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8 [ Time Frame: Part 1: Baseline (pre-dose Day 1), Week 8 ] [ Designated as safety issue: No ]
    BMI was defined as weight in kilogram (kg) divided by height in meters^2 (m^2). Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
  • Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit) [ Time Frame: Baseline (pre-dose Week 12), Week 36 ] [ Designated as safety issue: No ]
    BMI was defined as weight in kg divided by height in m^2. Change in BMI over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
  • Part 1: Change From Baseline in Sweat Chloride Through Week 8 [ Time Frame: Part 1: Baseline (pre-dose Day 1), Week 8 ] [ 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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
  • Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit) [ Time Frame: Baseline (pre-dose Week 12), Week 36 ] [ 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 in sweat chloride over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
  • Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 [ Time Frame: Part 1: Baseline (pre-dose Day 1), Week 8 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated patient-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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
  • Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit) [ Time Frame: Baseline (pre-dose Week 12), Week 36 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated patient-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. Change in CFQ-R respiratory domain score over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
  • Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part 1: From signing of informed consent up to Week 20 ] [ Designated as safety issue: Yes ]
    AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment 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.
  • Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part 2: Week 20 up to Week 40 ] [ Designated as safety issue: Yes ]
    AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment 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.
  • Change from baseline in body mass index (BMI) [ Time Frame: At 8 weeks and 24 weeks of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in sweat chloride [ Time Frame: Through 8 weeks and 24 weeks of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in the respiratory domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) [ Time Frame: Through 8 weeks and 24 weeks of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation
A Phase 3, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Crossover Study With an Open-Label Period to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation

The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cystic Fibrosis
  • Drug: Ivacaftor
    150 mg tablet, oral use, administered twice a day (q12h)
    Other Names:
    • Kalydeco
    • VX-770
  • Drug: Placebo
    oral use, administered twice a day (q12h)
  • Experimental: Part 1: Ivacaftor First, Then Placebo
    Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Interventions:
    • Drug: Ivacaftor
    • Drug: Placebo
  • Experimental: Part 1: Placebo First, Then Ivacaftor
    Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.
    Interventions:
    • Drug: Ivacaftor
    • Drug: Placebo
  • Experimental: Part 2: Ivacaftor
    Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
    Intervention: Drug: Ivacaftor
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
39
October 2013
October 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female with confirmed diagnosis of CF
  • At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D
  • Percent predicted forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) 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:

  • G551D-CFTR mutation on at least 1 allele
  • 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
  • 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
  • Use of inhaled hypertonic saline treatment
  • Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
  • Evidence of cataract or lens opacity at screening
Both
6 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   France
 
NCT01614470
VX12-770-111
Yes
Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation Therapeutics
Principal Investigator: Christine De Boeck, MD, PhD University of Leuven
Vertex Pharmaceuticals Incorporated
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP