Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation
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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 |
- 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 ]
- 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: | February 2013 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
-
Drug: VX-770
Eligibility| Ages Eligible for Study: | 12 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| United States, Virginia | |
| Charlottesville, Virginia, United States | |
| 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 4, 2012 |
| 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 May 19, 2013