Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    VX16-445-001
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03227471
Recruitment Status : Completed
First Posted : July 24, 2017
Results First Posted : January 18, 2022
Last Update Posted : January 18, 2022
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: IVA Drug: TEZ/IVA Drug: VX-445 Drug: Matched Placebo Drug: TEZ Drug: VX-561 Phase 1 Phase 2

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Actual Study Start Date : January 23, 2017
Actual Primary Completion Date : March 27, 2018
Actual Study Completion Date : March 27, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Placebo Comparator: Part A: Pooled Placebo (Except Cohort A7)
Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
 Drug: Matched Placebo
Matched placebo.
Experimental: Part A: VX-445 (Except Cohort A7)
Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.
 Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Experimental: Part A: VX-445 (Cohort A7)
Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.
 Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor

Drug: VX-445
VX-445 IV injection
Other Names:
  • ELX
  • elexacaftor
Placebo Comparator: Part B: Pooled Placebo (Cohort B1 to B4)
Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.
 Drug: Matched Placebo
Matched placebo.
Experimental: Part B: VX-445 (Cohort B1 to B4)
Participants without CF who received VX-445 tablet qd for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
 Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Placebo Comparator: Part C: Pooled Placebo (Cohort C1 to C3)
Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) qd in the morning and placebo matched to IVA in the evening for 14 days.
 Drug: Matched Placebo
Matched placebo.
Experimental: Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
 Drug: IVA
IVA tablet for oral administration
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Placebo Comparator: Part D: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA qd in the evening for 4 weeks in the TC treatment period.
 Drug: Matched Placebo
Matched placebo.
Experimental: Part D: VX-445/TEZ/IVA TC - Low Dose
Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
 Drug: IVA
IVA tablet for oral administration
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Experimental: Part D: VX-445/TEZ/IVA TC - Medium Dose
Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
 Drug: IVA
IVA tablet for oral administration
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Experimental: Part D: VX-445/TEZ/IVA TC - High Dose
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
 Drug: IVA
IVA tablet for oral administration
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Active Comparator: Part E: TEZ/IVA
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
 Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor
Experimental: Part E: VX-445/TEZ/IVA TC
Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
 Drug: IVA
IVA tablet for oral administration
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor

Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor
Placebo Comparator: Part F: Placebo
Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
 Drug: Matched Placebo
Matched placebo.
Experimental: Part F: VX-445/TEZ/VX-561 TC
Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
 Drug: VX-445
VX-445 tablet for oral administration.
Other Names:
  • ELX
  • elexacaftor

Drug: TEZ
Tablet for oral administration.
Other Names:
  • VX-661
  • tezacaftor

Drug: VX-561
Tablet for oral administration.
Other Name: CTP-656


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 Outcome Measures :
  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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03227471


Locations
Show Show 38 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] August 8, 2017
Statistical Analysis Plan  [PDF] October 6, 2017

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03227471    
Other Study ID Numbers: VX16-445-001
2017-000797-11 ( EudraCT Number )
First Posted: July 24, 2017    Key Record Dates
Results First Posted: January 18, 2022
Last Update Posted: January 18, 2022
Last Verified: December 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Elexacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action