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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03227471




Registration number
NCT03227471
Ethics application status
Date submitted
18/07/2017
Date registered
24/07/2017
Date last updated
18/01/2022

Titles & IDs
Public title
A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Scientific title
A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
Secondary ID [1] 0 0
2017-000797-11
Secondary ID [2] 0 0
VX16-445-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IVA
Treatment: Drugs - TEZ/IVA
Treatment: Drugs - VX-445
Treatment: Drugs - Matched Placebo
Treatment: Drugs - TEZ
Treatment: Drugs - VX-561
Treatment: Drugs - VX-445

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.


Treatment: Drugs: IVA
IVA tablet for oral administration

Treatment: Drugs: TEZ/IVA
TEZ/IVA fixed-dose combination for oral administration.

Treatment: Drugs: VX-445
VX-445 tablet for oral administration.

Treatment: Drugs: Matched Placebo
Matched placebo.

Treatment: Drugs: TEZ
Tablet for oral administration.

Treatment: Drugs: VX-561
Tablet for oral administration.

Treatment: Drugs: VX-445
VX-445 IV injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
Primary outcome [2] 0 0
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Primary outcome [3] 0 0
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [3] 0 0
From Baseline through Day 29
Primary outcome [4] 0 0
Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [4] 0 0
From Baseline through Day 29
Primary outcome [5] 0 0
Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [5] 0 0
From Baseline through Day 29
Secondary outcome [1] 0 0
Part A: Maximum Observed Concentration (Cmax) of VX-445
Timepoint [1] 0 0
Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Secondary outcome [2] 0 0
Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Timepoint [2] 0 0
Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose
Secondary outcome [3] 0 0
Part B: Maximum Observed Concentration (Cmax) of VX-445
Timepoint [3] 0 0
Pre-dose to 96 hours post-dose on Day 1 and Day 10
Secondary outcome [4] 0 0
Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Timepoint [4] 0 0
Pre-dose to 96 hours post-dose on Day 1 and Day 10
Secondary outcome [5] 0 0
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Timepoint [5] 0 0
Pre-dose on Day 10
Secondary outcome [6] 0 0
Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Timepoint [6] 0 0
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Secondary outcome [8] 0 0
Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Timepoint [8] 0 0
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Secondary outcome [9] 0 0
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)
Timepoint [9] 0 0
Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14
Secondary outcome [10] 0 0
Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Timepoint [10] 0 0
Pre-dose on Day 7 and Day 14
Secondary outcome [11] 0 0
Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Timepoint [11] 0 0
Pre-dose on Day 7 and Day 14
Secondary outcome [12] 0 0
Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
Timepoint [12] 0 0
Pre-dose on Day 15 and Day 29
Secondary outcome [13] 0 0
Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
Timepoint [13] 0 0
Pre-dose on Day 15 and Day 29
Secondary outcome [14] 0 0
Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
Timepoint [14] 0 0
Pre-dose on Day 15 and Day 29
Secondary outcome [15] 0 0
Part D: Absolute Change in Sweat Chloride Concentration
Timepoint [15] 0 0
From Baseline through Day 29
Secondary outcome [16] 0 0
Part E: Absolute Change in Sweat Chloride Concentration
Timepoint [16] 0 0
From Baseline through Day 29
Secondary outcome [17] 0 0
Part F: Absolute Change in Sweat Chloride Concentration
Timepoint [17] 0 0
From Baseline through Day 29
Secondary outcome [18] 0 0
Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [18] 0 0
From Baseline through Day 29
Secondary outcome [19] 0 0
Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [19] 0 0
From Baseline through Day 29
Secondary outcome [20] 0 0
Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [20] 0 0
From Baseline through Day 29
Secondary outcome [21] 0 0
Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Timepoint [21] 0 0
From Baseline through Day 29
Secondary outcome [22] 0 0
Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Timepoint [22] 0 0
From Baseline through Day 29
Secondary outcome [23] 0 0
Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Timepoint [23] 0 0
From Baseline through Day 29

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Center - Clayton
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
The Royal Children's Hospital Melbourne - Parkville
Recruitment hospital [4] 0 0
Mater Adult Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [6] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment postcode(s) [4] 0 0
- Brisbane
Recruitment postcode(s) [5] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Vermont
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Belgium
State/province [20] 0 0
Edegem
Country [21] 0 0
Belgium
State/province [21] 0 0
Gent
Country [22] 0 0
Netherlands
State/province [22] 0 0
Amsterdam
Country [23] 0 0
Netherlands
State/province [23] 0 0
Den Haag
Country [24] 0 0
Netherlands
State/province [24] 0 0
Nijmegen
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.