Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01161537
First received: July 9, 2010
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The encoded protein, CFTR, is an epithelial chloride ion channel responsible for aiding in the regulation of salt and water absorption and secretion in various tissues. Although the disease affects multiple organs, the leading cause of mortality is the progressive loss of lung function. Obstruction of airways with thick mucous, chronic bacterial infection of the airways, and inflammatory response are all thought to play a role in causing lung damage. Through its function as a chloride channel, CFTR is believed to be integral in epithelial ion and water transport and hence, maintaining the normal hydration of lung secretions.

VX-770 is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR. Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, VX-770 has been selected for clinical development as a possible treatment for patients with CF.

Hyperpolarized noble gas magnetic resonance imaging (HG-MRI) is a promising new means of assessing lung function by direct imaging of certain non-radioactive isotopes of an inert noble gas, such as helium or xenon. Through this technique, high-resolution 3-dimensional images of lung ventilation can be obtained in both pediatric and adult patients during a single short breath-hold following inhalation of the gas.

This is a 2-part study to evaluate the effect of VX-770 on hyperpolarized 3He-MRI, and to evaluate the safety and efficacy of VX-770 in subjects aged 12 years and older with CF who have the G551D-CFTR mutation. Part A is a single-blind, placebo-controlled study that includes 4 weeks of VX-770 treatment and 4 weeks of placebo treatment. Part B is an open-label, 48 week study of long-term effect of VX 770 on hyperpolarized 3He-MRI.


Condition Intervention Phase
Cystic Fibrosis
Drug: VX-770
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase 2, Single-Blind, Placebo-Controlled Study to Evaluate the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis, the G551D Mutation, and FEV1 ≥40% Predicted

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Part A: Change in total ventilation defect defined by 3He-MRI [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Part B: Change in total ventilation defect defined by 3He-MRI [ Time Frame: Baseline through 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part A: Safety as determined by adverse events, clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard digital electrocardiograms (ECGs), and vital signs [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Part A: Efficacy as measured by change in in percent predicted FEV1, Sweat Chloride, and CF Questionnaire-Revised (CFQ-R) score [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Part B: Safety as determined by adverse events, clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard digital electrocardiograms (ECGs), and vital signs [ Time Frame: Baseline through 48 weeks ] [ Designated as safety issue: Yes ]
  • Part B: Efficacy as measured by change in in percent predicted FEV1, Sweat Chloride, and CF Questionnaire-Revised (CFQ-R) score [ Time Frame: Baseline through 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: October 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: VX-770
    150 mg Tablet, oral use, twice daily every 12 hours (q12h)
    Drug: Placebo
    Tablet, oral use, twice daily every 12 hours (q12h)
  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female with Cystic Fibrosis
  • Must have the G551D-CFTR mutation on at least 1 allele
  • FEV1 ≥40% of predicted normal for age, gender, and height at Screening
  • 12 years of age or older
  • Must be able to swallow tablets

Exclusion Criteria:

  • History of solid organ or hematological transplantation
  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
  • Use of inhaled hypertonic saline treatment within 14 days prior to the Screening Visit
  • Extensive body tattoos or other physical features that will confound MRI
  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: NCT01161537

Locations
United States, Virginia
Charlottesville, Virginia, United States
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Talissa Altes, MD University of Virginia
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01161537     History of Changes
Other Study ID Numbers: VX10-770-107
Study First Received: July 9, 2010
Last Updated: June 11, 2013
Health Authority: United States: Food and Drug Administration

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 22, 2014