Cystic FibrosisPhase 1/2NCT03227471
A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
A Phase 1/2 study testing IVA, TEZ/IVA and VX-445 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 38 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- IVA, TEZ/IVA and VX-445
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 225 participants
- Where
- 38 sitesin 4 countries
- Study dates
- 23 Jan 2017to 27 Mar 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
38 sites in 4 countries.
38 sites in 4 countries
United States26 sites
University of New Mexico School of Medicine
Albuquerque, New Mexico, 87131
Children's Specialty Services at North Druid Hills
Atlanta, Georgia, 30324
Austin Children's Chest Associates
Austin, Texas, 78723
The University of Vermont
Burlington, Vermont, 05401
University of Virginia Health System
Charlottesville, Virginia, 22908
Northwestern Memorial Hospital
Chicago, Illinois, 60611
UC Health Office of Clinical Research
Cincinnati, Ohio, 45267
University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
National Jewish Health
Denver, Colorado, 80206
Harper University Hospital
Detroit, Michigan, 48201
Covance Clinical Research Unit Inc., Evansville Clinic [Parts A, B, C only]
Evansville, Indiana, 47710
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Valley Children's Healthcare
Madera, California, 93636
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
Minneapolis, Minnesota, 55404
West Virginia University Hospitals
Morgantown, Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
Tulane Medical Center
New Orleans, Louisiana, 70112
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
(Kaiser Permanente) Oakland Medical Center
Oakland, California, 96411
Central Florida Pulmonary Group
Orlando, Florida, 32803
Virginia Commonwealth University
Richmond, Virginia, 23298
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606
Banner University of Arizona Medical Center
Tucson, Arizona, 85724
Australia6 sites
Mater Adult Hospital
Brisbane
Monash Medical Center
Clayton, Victoria
The Alfred Hospital
Melbourne, Victoria
The Royal Children's Hospital Melbourne
Parkville, Victoria
Royal Prince Alfred Hospital
Sydney
Westmead Hospital
Sydney
Netherlands4 sites
Academic Medical Centre
Amsterdam
Radboud UMC
Nijmegen
Erasmus Medical Center
Rotterdam
HagaZiekenhuis van den Haag
The Hague
Belgium2 sites
Antwerp University Hospital
Edegem
Universitair Ziekenhuis Gent
Ghent
About this study
Official title: A Phase 1/2 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).
- Conditions
- Cystic Fibrosis
- Being tested
- IVA, TEZ/IVA, VX-445, Matched Placebo, TEZ
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVADrug
Also called VX-770, ivacaftor
IVA tablet for oral administration
TEZ/IVADrug
Also called VX-661/VX-770, tezacaftor/ivacaftor
TEZ/IVA fixed-dose combination for oral administration.
VX-445Drug
Also called ELX, elexacaftor
VX-445 tablet for oral administration.
Matched PlaceboDrug
Matched placebo.
TEZDrug
Also called VX-661, tezacaftor
Tablet for oral administration.
VX-561Drug
Also called CTP-656
Tablet for oral administration.
VX-445Drug
Also called ELX, elexacaftor
VX-445 IV injection
| Study group | Role | What they receive |
|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Placebo comparator | Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5. Receives: Drug: Matched Placebo |
| Part A: VX-445 (Except Cohort A7) | Experimental | 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. Receives: Drug: VX-445 |
| Part A: VX-445 (Cohort A7) | Experimental | 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. Receives: Drug: VX-445 |
| Part B: Pooled Placebo (Cohort B1 to B4) | Placebo comparator | Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4. Receives: Drug: Matched Placebo |
| Part B: VX-445 (Cohort B1 to B4) | Experimental | 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). Receives: Drug: VX-445 |
| Part C: Pooled Placebo (Cohort C1 to C3) | Placebo comparator | 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. Receives: Drug: Matched Placebo |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Experimental | 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. Receives: Drug: IVA; Drug: TEZ/IVA; Drug: VX-445 |
| Part D: Placebo | Placebo comparator | 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. Receives: Drug: Matched Placebo |
| Part D: VX-445/TEZ/IVA TC - Low Dose | Experimental | 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. Receives: Drug: IVA; Drug: TEZ/IVA; Drug: VX-445 |
| Part D: VX-445/TEZ/IVA TC - Medium Dose | Experimental | 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. Receives: Drug: IVA; Drug: TEZ/IVA; Drug: VX-445 |
| Part D: VX-445/TEZ/IVA TC - High Dose | Experimental | 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. Receives: Drug: IVA; Drug: TEZ/IVA; Drug: VX-445 |
| Part E: TEZ/IVA | Active comparator | 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. Receives: Drug: TEZ/IVA |
| Part E: VX-445/TEZ/IVA TC | Experimental | 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. Receives: Drug: IVA; Drug: TEZ/IVA; Drug: VX-445 |
| Part F: Placebo | Placebo comparator | Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period. Receives: Drug: Matched Placebo |
| Part F: VX-445/TEZ/VX-561 TC | Experimental | 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. Receives: Drug: VX-445; Drug: TEZ; Drug: VX-561 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Secondary outcomes (23)
Part A: Maximum Observed Concentration (Cmax) of VX-445
Measured: Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Measured: Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Part B: Maximum Observed Concentration (Cmax) of VX-445
Measured: Pre-dose to 96 hours post-dose on Day 1 and Day 10
Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Measured: Pre-dose to 96 hours post-dose on Day 1 and Day 10
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Measured: Pre-dose on Day 10
Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Measured: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
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)
Measured: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Measured: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
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)
Measured: Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Measured: Pre-dose on Day 7 and Day 14
Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Measured: Pre-dose on Day 7 and Day 14
Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
Measured: Pre-dose on Day 15 and Day 29
Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
Measured: Pre-dose on Day 15 and Day 29
Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
Measured: Pre-dose on Day 15 and Day 29
Part D: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Measured: From Baseline through Day 29
Part E: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Measured: From Baseline through Day 29
Part F: Absolute Change in Sweat Chloride Concentration
Sweat samples were collected using an approved collection device.
Measured: From Baseline through Day 29
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: From Baseline through Day 29
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
Measured: From Baseline through Day 29
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
Measured: From Baseline through Day 29
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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.
Measured: From Baseline through Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2017
- Study start23 Jan 2017
- Primary completion27 Mar 2018
- Study completion27 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03227471
- Sponsor's protocol ID
- VX16-445-001
- Other IDs
- 2017-000797-11, 2017
- Status last verified
- Dec 2021
- First submitted
- 18 Jul 2017
- Last updated
- 18 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PubMed 37983082Southern 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 33331662Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Sass LA, Tullis E, McKee CM, Moskowitz SM, Robertson S, Savage J, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Taylor-Cousar JL; VX16-445-001 Study Group. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1612-1620. doi: 10.1056/NEJMoa1807120. Epub 2018 Oct 18.
PubMed 30334692
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03227471
- Acronym / sponsor ID
- VX16-445-001
- Conditions
- Cystic Fibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 23 Jan 2017 (actual)
- Primary completion
- 27 Mar 2018 (actual)
- Study completion
- 27 Mar 2018 (actual)
- First posted
- 24 Jul 2017 (actual)
- Results
- Posted 18 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Part A: Pooled Placebo (Except Cohort A7) | Placebo comparator | Drug: Matched PlaceboParticipants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5. |
| Part A: VX-445 (Except Cohort A7) | Experimental | Drug: VX-445Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5. |
| Part A: VX-445 (Cohort A7) | Experimental | Drug: VX-445Participants 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. |
| Part B: Pooled Placebo (Cohort B1 to B4) | Placebo comparator | Drug: Matched PlaceboParticipants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4. |
| Part B: VX-445 (Cohort B1 to B4) | Experimental | Drug: VX-445Participants 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). |
| Part C: Pooled Placebo (Cohort C1 to C3) | Placebo comparator | Drug: Matched PlaceboParticipants 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. |
| Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) | Experimental | Drug: IVA, Drug: TEZ/IVA, Drug: VX-445Participants 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. |
| Part D: Placebo | Placebo comparator | Drug: Matched PlaceboParticipants 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. |
| Part D: VX-445/TEZ/IVA TC - Low Dose | Experimental | Drug: IVA, Drug: TEZ/IVA, Drug: VX-445Participants 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. |
| Part D: VX-445/TEZ/IVA TC - Medium Dose | Experimental | Drug: IVA, Drug: TEZ/IVA, Drug: VX-445Participants 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. |
| Part D: VX-445/TEZ/IVA TC - High Dose | Experimental | Drug: IVA, Drug: TEZ/IVA, Drug: VX-445Participants 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. |
| Part E: TEZ/IVA | Active comparator | Drug: TEZ/IVAFollowing 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. |
| Part E: VX-445/TEZ/IVA TC | Experimental | Drug: IVA, Drug: TEZ/IVA, Drug: VX-445Following 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. |
| Part F: Placebo | Placebo comparator | Drug: Matched PlaceboParticipants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period. |
| Part F: VX-445/TEZ/VX-561 TC | Experimental | Drug: VX-445, Drug: TEZ, Drug: VX-561Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- Body weight ≥35 kg.
- Subjects must have an eligible CFTR genotype:
Key exclusion criteria (10 listed)
- 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.
- History of clinically significant cirrhosis with or without portal hypertension.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVAAlso: VX-770, ivacaftorIVA tablet for oral administration | Drug | Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3), Part D: VX-445/TEZ/IVA TC - High Dose, Part D: VX-445/TEZ/IVA TC - Low Dose, Part D: VX-445/TEZ/IVA TC - Medium Dose, Part E: VX-445/TEZ/IVA TC |
| TEZ/IVAAlso: VX-661/VX-770, tezacaftor/ivacaftorTEZ/IVA fixed-dose combination for oral administration. | Drug | Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3), Part D: VX-445/TEZ/IVA TC - High Dose, Part D: VX-445/TEZ/IVA TC - Low Dose, Part D: VX-445/TEZ/IVA TC - Medium Dose, Part E: TEZ/IVA, Part E: VX-445/TEZ/IVA TC |
| VX-445Also: ELX, elexacaftorVX-445 tablet for oral administration. | Drug | Part A: VX-445 (Cohort A7), Part A: VX-445 (Except Cohort A7), Part B: VX-445 (Cohort B1 to B4), Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3), Part D: VX-445/TEZ/IVA TC - High Dose, Part D: VX-445/TEZ/IVA TC - Low Dose, Part D: VX-445/TEZ/IVA TC - Medium Dose, Part E: VX-445/TEZ/IVA TC, Part F: VX-445/TEZ/VX-561 TC |
| Matched PlaceboMatched placebo. | Drug | Part A: Pooled Placebo (Except Cohort A7), Part B: Pooled Placebo (Cohort B1 to B4), Part C: Pooled Placebo (Cohort C1 to C3), Part D: Placebo, Part F: Placebo |
| TEZAlso: VX-661, tezacaftorTablet for oral administration. | Drug | Part F: VX-445/TEZ/VX-561 TC |
| VX-561Also: CTP-656Tablet for oral administration. | Drug | Part F: VX-445/TEZ/VX-561 TC |
| VX-445Also: ELX, elexacaftorVX-445 IV injection | Drug | Part A: VX-445 (Cohort A7) |
Primary outcome
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)
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)
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.
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.
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.
23 secondary outcomes
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
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
Part B: Maximum Observed Concentration (Cmax) of VX-445
Time frame: Pre-dose to 96 hours post-dose on Day 1 and Day 10
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
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Time frame: Pre-dose on Day 10
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
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
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
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
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
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
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
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
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
Part D: Absolute Change in Sweat Chloride Concentration
Time frame: From Baseline through Day 29
Part E: Absolute Change in Sweat Chloride Concentration
Time frame: From Baseline through Day 29
Part F: Absolute Change in Sweat Chloride Concentration
Time frame: From Baseline through Day 29
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline through Day 29
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline through Day 29
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline through Day 29
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline through Day 29
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline through Day 29
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline through Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37983082Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
- Derived from this study: PubMed 33331662Southern 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.
- Derived from this study: PubMed 30334692Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Sass LA, Tullis E, McKee CM, Moskowitz SM, Robertson S, Savage J, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Taylor-Cousar JL; VX16-445-001 Study Group. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1612-1620. doi: 10.1056/NEJMoa1807120. Epub 2018 Oct 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
38 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IVA, TEZ/IVA and VX-445 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 38 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Australia, Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03227471, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2022.