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

NCT ID: NCT01161537

Last Updated: 2014-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-02-28

Brief Summary

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 mucus, 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 (ivacaftor) 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 helium-3 magnetic resonance imaging (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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

VX-770

Part A: Subjects received placebo tablets matched to VX-770 150 milligram (mg) orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study.

Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.

Group Type: EXPERIMENTAL

VX-770

Intervention Type: DRUG

Tablet.

Placebo

Intervention Type: DRUG

Tablet.

Interventions

VX-770

Tablet.

Intervention Type: DRUG

Placebo

Tablet.

Intervention Type: DRUG

Other Intervention Names

Ivacaftor

Eligibility 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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Talissa Altes, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

Charlottesville, Virginia, United States

Countries

United States

References

Altes TA, Johnson M, Fidler M, Botfield M, Tustison NJ, Leiva-Salinas C, de Lange EE, Froh D, Mugler JP 3rd. Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis. J Cyst Fibros. 2017 Mar;16(2):267-274. doi: 10.1016/j.jcf.2016.12.004. Epub 2017 Jan 26.

Reference Type: DERIVED

PMID: 28132845 (View on PubMed)

Other Identifiers

VX10-770-107

Identifier Type: -

Identifier Source: org_study_id