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
  Purpose

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).


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

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

Resource links provided by NLM:


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) [ Time Frame: Through 8 weeks and 24 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 39
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: Treatment Sequence 2
Placebo in Treatment Period 1 -> washout -> Ivacaftor 150mg q12h in Treatment Period 2 -> Open-label Treatment Period
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 1
Ivacaftor 150mg q12h in Treatment Period 1 -> washout -> Placebo in Treatment Period 2 -> Open-label Treatment Period
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)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01614470

Locations
United States, Florida
Tampa, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
St. Louis, Missouri, United States
United States, Texas
Houston, Texas, United States
Belgium
Leuven, Belgium
France
Lyon, France
Montpellier, France
Paris, France
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Christine De Boeck, MD, PhD University of Leuven
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01614470     History of Changes
Other Study ID Numbers: VX12-770-111
Study First Received: June 5, 2012
Last Updated: January 13, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 23, 2014