Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of VX-809 to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of VX-809 in Cystic Fibrosis Subjects Homozygous for the ∆F508-CFTR Gene Mutation

The primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: VX-809

Detailed Description

This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del. Enrollment was planned for 90 participants at approximately 20 centers. Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design. Participants were outpatients during the study, except for overnight stays on Day 1 and 28.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
  • Leuven, Belgium
• Canada
  • Ontario
    • Toronto, Ontario, Canada
• Germany
  • Cologne, Germany
  • Hannover, Germany
• Netherlands
  • Rotterdam, Netherlands
  • Utrecht, Netherlands
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • California
    • Palo Alto, California, United States
    • San Diego, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Iowa
    • Iowa City, Iowa, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • St. Louis, Missouri, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
• Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
• Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
• Screening laboratory values, tests, and physical examination within acceptable ranges
• Negative pregnancy test (for women of child-bearing potential)
• Able and willing to follow contraceptive requirements
• Willing to remain on a stable medication regimen for the duration of study participation

Exclusion Criteria:

• History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
• Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
• Impaired hepatic or renal function
• History of organ or hematological transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matched to VX-809 capsule orally once daily for 28 days.	Drug: Placebo; Placebo matched to VX-809 capsules.
Experimental: VX-809, 25 mg; VX-809, 25 milligram (mg) capsule orally once daily for 28 days.	Drug: VX-809; Capsules
Experimental: VX-809, 50 mg; VX-809, 50 mg capsule orally once daily for 28 days.	Drug: VX-809; Capsules
Experimental: VX-809, 100 mg; VX-809, 100 mg capsule orally once daily for 28 days.	Drug: VX-809; Capsules
Experimental: VX-809, 200 mg; VX-809, 200 mg capsule orally once daily for 28 days.	Drug: VX-809; Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability Based on Adverse Events (AEs)	AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. Serious adverse event (SAE) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.	Up to 14 days after last dose (last dose = Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 28
Change From Baseline in Percent Predicted FEV1 at Day 28	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.	Baseline, Day 28
Change From Baseline in Forced Vital Capacity (FVC) at Day 28	FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.	Baseline, Day 28
Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28	FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).	Baseline, Day 28
Change From Baseline in Sweat Chloride at Day 28	Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.	Baseline, Day 28
Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28	Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported. NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe".	Baseline, Day 28
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	Baseline, Day 28
Maximum Plasma Concentration (Cmax) of VX-809	Only participants who received VX-809 were analyzed for this outcome measure.	Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose)
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809	Only participants who received VX-809 were analyzed for this outcome measure.	Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose)

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12:CD010966. doi: 10.1002/14651858.CD010966.pub3.
• Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA, Ballmann M, Boyle MP, Bronsveld I, Campbell PW, De Boeck K, Donaldson SH, Dorkin HL, Dunitz JM, Durie PR, Jain M, Leonard A, McCoy KS, Moss RB, Pilewski JM, Rosenbluth DB, Rubenstein RC, Schechter MS, Botfield M, Ordonez CL, Spencer-Green GT, Vernillet L, Wisseh S, Yen K, Konstan MW. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012 Jan;67(1):12-8. doi: 10.1136/thoraxjnl-2011-200393. Epub 2011 Aug 8.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: March 18, 2009
• First Submitted That Met QC Criteria: March 18, 2009
• First Posted (Estimate): March 19, 2009

Study Record Updates

• Last Update Posted (Estimate): August 28, 2015
• Last Update Submitted That Met QC Criteria: August 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: CFTR; Pancreatic diseases; Lung diseases; ∆F508; F508del; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic disease, inborn; Infant, newborn, diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: VX08-809-101