Clinical trial NCT01161537: Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2010-07-13
Enrollment: 13
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43
timeFrame: Part A: Baseline (pre-dose Day 15), Day 43
measure: Part B: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Week 48
timeFrame: Part B: Baseline (Day -1), Week 48
Secondary outcomes:
measure: Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
timeFrame: Part A: Day 1 up to Day 57
measure: Part A: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Day 43
timeFrame: Part A: Baseline (pre-dose Day 15), Day 43
measure: Part A: Absolute Change From Baseline in Sweat Chloride at Day 43
timeFrame: Part A: Baseline (pre-dose Day 15), Day 43
measure: Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Day 43
timeFrame: Baseline (pre-dose Day 15), Day 43
measure: Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
timeFrame: Part B: Day 1 up to Week 48
measure: Part B: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 48
timeFrame: Part B: Baseline (Day -1), Week 48
measure: Part B: Absolute Change From Baseline in Sweat Chloride at Week 48
timeFrame: Part B: Baseline (Day -1), Week 48
measure: Part B: Absolute Change From Baseline in in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Week 48
timeFrame: Part B: Baseline (Day -1), Week 48
Other outcomes:
Locations:
city: Charlottesville
country: United States
state: Virginia
Study officials:
affiliation: University of Virginia
name: Talissa Altes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.