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

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01614470
First received: June 5, 2012
Last updated: January 13, 2014
Last verified: January 2014

June 5, 2012
January 13, 2014
July 2012
October 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01614470 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Study of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D 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 patients with CF. Results from Phase 3 studies (VX08-770-102 [Study 102] and VX08-770-103 [Study 103]) showed that ivacaftor is effective in the treatment of patients 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 patients 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: Treatment Sequence 2
    Placebo in Treatment Period 1 -> washout -> Ivacaftor 150mg q12h in Treatment Period 2 -> Open-label Treatment Period
    Interventions:
    • Drug: Ivacaftor
    • Drug: Placebo
  • Experimental: Treatment Sequence 1
    Ivacaftor 150mg q12h in Treatment Period 1 -> washout -> Placebo in Treatment Period 2 -> Open-label Treatment Period
    Interventions:
    • Drug: Ivacaftor
    • Drug: Placebo
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
  • FEV1 ≥ 40% predicted normal for age, sex, and height
  • 6 years of age or older
  • Minimum weight of 15 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 P450 (CYP) 3A
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
Principal Investigator: Christine De Boeck, MD, PhD University of Leuven
Vertex Pharmaceuticals Incorporated
January 2014

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