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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 13
- Primary Endpoint
- Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- 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
Arms & Interventions
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.
Intervention: VX-770 (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43
Time Frame: Part A: Baseline (pre-dose Day 15), Day 43
Subjects inhaled hyperpolarized helium-3 (3He) gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid magnetic resonance imaging (MRI) was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He-MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42).
Part B: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Week 48
Time Frame: Part B: Baseline (Day -1), Week 48
Subjects were asked to inhale hyperpolarized 3 He gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid MRI was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks).
Secondary Outcomes
- Part B: Absolute Change From Baseline in Sweat Chloride at Week 48(Part B: Baseline (Day -1), Week 48)
- Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs(Part A: Day 1 up to Day 57)
- Part A: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Day 43(Part A: Baseline (pre-dose Day 15), Day 43)
- Part A: Absolute Change From Baseline in Sweat Chloride at Day 43(Part A: Baseline (pre-dose Day 15), Day 43)
- Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Day 43(Baseline (pre-dose Day 15), Day 43)
- Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs(Part B: Day 1 up to Week 48)
- Part B: Absolute Change From Baseline in in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Week 48(Part B: Baseline (Day -1), Week 48)
- Part B: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 48(Part B: Baseline (Day -1), Week 48)