Phase 2
N=8
Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation
Cystic Fibrosis
Bottom Line
View on ClinicalTrials.gov: NCT01161537 ↗Enrolled (actual)
8
Serious AEs
4.0%
Results posted
Jul 2014
Primary outcome: Primary: Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43 — -8.20 percentage of total lung volume
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- VX-770 (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Primary completion
- Feb 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43 |
-8.20 | — |
| PRIMARY Part B: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Week 48 |
-6.33 | — |
| SECONDARY Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs |
2; 3; 0; 0; 0; 0 | — |
| SECONDARY Part A: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Day 43 |
12.78 | — |
| SECONDARY Part A: Absolute Change From Baseline in Sweat Chloride at Day 43 |
-42.31 | — |
| SECONDARY Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Day 43 |
-7.64 | — |
| SECONDARY Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs |
6; 1; 4 | — |
| SECONDARY Part B: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 48 |
5.17 | — |
| SECONDARY Part B: Absolute Change From Baseline in Sweat Chloride at Week 48 |
-48.88 | — |
| SECONDARY Part B: Absolute Change From Baseline in in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Week 48 |
15.08 | — |
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
Data sourced from ClinicalTrials.gov (NCT01161537). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.