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

Browse trials for

• Cystic Fibrosis 1,581
• Fibrosis 3,255

Keywords

• ∆F508
• F508del
• Cystic Fibrosis Transmembrane Conductance Regulator
• CFTR
• Pancreatic diseases
• Lung diseases
• Genetic disease, inborn
• Infant, newborn, diseases

Cystic Fibrosis

1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.

This study's enrollment of 93 is above the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.

Lead sponsor

Vertex Pharmaceuticals Incorporated is the lead sponsor of 243 studies on the registry; 19 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 49 (48%) have results posted.

Study arms

• Placebo comparator
  Placebo

  Placebo matched to VX-809 capsule orally once daily for 28 days.

  Drug: Placebo

• Experimental
  VX-809, 25 mg

  VX-809, 25 milligram (mg) capsule orally once daily for 28 days.

  Drug: VX-809

• Experimental
  VX-809, 50 mg

  VX-809, 50 mg capsule orally once daily for 28 days.

  Drug: VX-809

• Experimental
  VX-809, 100 mg

  VX-809, 100 mg capsule orally once daily for 28 days.

  Drug: VX-809

• Experimental
  VX-809, 200 mg

  VX-809, 200 mg capsule orally once daily for 28 days.

  Drug: VX-809

Interventions

• DrugVX-809

  Capsules

• DrugPlacebo

  Placebo matched to VX-809 capsules.

Primary outcomes

1. 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.

   Time frame: Up to 14 days after last dose (last dose = Day 28)

Secondary outcomes

1. 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.

   Time frame: Baseline, Day 28

2. 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.

   Time frame: Baseline, Day 28

3. 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.

   Time frame: Baseline, Day 28

4. 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).

   Time frame: Baseline, Day 28

5. 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.

   Time frame: Baseline, Day 28

6. 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".

   Time frame: Baseline, Day 28

7. 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.

   Time frame: Baseline, Day 28

8. Maximum Plasma Concentration (Cmax) of VX-809

   Only participants who received VX-809 were analyzed for this outcome measure.

   Time frame: 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)

9. 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.

   Time frame: 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)

Baseline characteristics

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(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. PubMed 33331662 ↗
• 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. PubMed 21825083 ↗