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Completed

NCT Number: NCT03227471

A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C were conducted in healthy subjects. Parts D, E, and F were conducted in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Monash Medical Center, Clayton, Victoria, Australia

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

Parts A, B, and C:

  • Female subjects must be of non-childbearing potential.
  • Between the ages of 18 and 55 years, inclusive.
  • Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

Parts D, E, and F:

  • Body weight ≥35 kg.
  • Subjects must have an eligible CFTR genotype:
  • Parts D and F: Heterozygous for F508del and an MF mutation (F/MF)
  • Part E: Homozygous for F508del (F/F)
  • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height.

Key Exclusion Criteria:

Parts A, B, and C:

  • Any condition possibly affecting drug absorption.
  • History of febrile illness within 14 days before the first study drug dose.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Parts D, E, and F:

  • History of clinically significant cirrhosis with or without portal hypertension.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Lung infection with organisms associated with a more rapid decline in pulmonary status.
  • History of solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Treatment and study plan

IVA

Drug

IVA tablet for oral administration

Other names: VX-770, ivacaftor

TEZ/IVA

Drug

TEZ/IVA fixed-dose combination for oral administration.

Other names: VX-661/VX-770, tezacaftor/ivacaftor

VX-445

Drug

VX-445 tablet for oral administration.

Other names: ELX, elexacaftor

Matched placebo

Drug

Matched placebo.

TEZ

Drug

Tablet for oral administration.

Other names: VX-661, tezacaftor

VX-561

Drug

Tablet for oral administration.

Other names: CTP-656

Primary outcomes

  1. Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: From first dose of study drug in treatment period up to safety follow-up (up to 28 days)

  2. Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)

  3. Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  4. Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  5. Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary outcomes

  1. Part A: Maximum Observed Concentration (Cmax) of VX-445

    Time frame: Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose

  2. Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445

    Time frame: Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose

  3. Part B: Maximum Observed Concentration (Cmax) of VX-445

    Time frame: Pre-dose to 96 hours post-dose on Day 1 and Day 10

  4. Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445

    Time frame: Pre-dose to 96 hours post-dose on Day 1 and Day 10

  5. Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445

    Time frame: Pre-dose on Day 10

  6. Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)

    Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

  7. Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)

    Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

  8. Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)

    Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

  9. Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA)

    Time frame: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

  10. Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)

    Time frame: Pre-dose on Day 7 and Day 14

  11. Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)

    Time frame: Pre-dose on Day 7 and Day 14

  12. Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)

    Time frame: Pre-dose on Day 15 and Day 29

  13. Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)

    Time frame: Pre-dose on Day 15 and Day 29

  14. Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561

    Time frame: Pre-dose on Day 15 and Day 29

  15. Part D: Absolute Change in Sweat Chloride Concentration

    Time frame: From Baseline through Day 29

    Sweat samples were collected using an approved collection device.

  16. Part E: Absolute Change in Sweat Chloride Concentration

    Time frame: From Baseline through Day 29

    Sweat samples were collected using an approved collection device.

  17. Part F: Absolute Change in Sweat Chloride Concentration

    Time frame: From Baseline through Day 29

    Sweat samples were collected using an approved collection device.

  18. Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  19. Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  20. Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Day 29

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  21. Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    Time frame: From Baseline through Day 29

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  22. Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    Time frame: From Baseline through Day 29

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  23. Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

    Time frame: From Baseline through Day 29

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Registry information

Official study title

A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jul 24, 2017
Registry last updated
Jan 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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