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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03525444




Registration number
NCT03525444
Ethics application status
Date submitted
2/05/2018
Date registered
15/05/2018
Date last updated
19/05/2020

Titles & IDs
Public title
A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Scientific title
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Secondary ID [1] 0 0
2018-000183-28
Secondary ID [2] 0 0
VX17-445-102
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 - VX-445/TEZ/IVA
Treatment: Drugs - IVA
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.

Experimental: VX-445/TEZ/IVA TC - Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.


Treatment: Drugs: VX-445/TEZ/IVA
Participants received VX-445/TEZ/IVA orally once daily in the morning.

Treatment: Drugs: IVA
Participants received IVA orally once daily in the evening

Treatment: Drugs: Placebo
Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.

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

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From Baseline at Week 4
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From Baseline through Week 24
Secondary outcome [2] 0 0
Number of Pulmonary Exacerbations (PEx) - Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Timepoint [2] 0 0
From Baseline through Week 24
Secondary outcome [3] 0 0
Absolute Change in Sweat Chloride (SwCl) - Sweat samples were collected using an approved collection device.
Timepoint [3] 0 0
From Baseline through Week 24
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From Baseline through Week 24
Secondary outcome [5] 0 0
Absolute Change in Body Mass Index (BMI) - BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Timepoint [5] 0 0
From Baseline at Week 24
Secondary outcome [6] 0 0
Absolute Change in Sweat Chloride - Sweat samples were collected using an approved collection device.
Timepoint [6] 0 0
From Baseline at Week 4
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
From Baseline at Week 4
Secondary outcome [8] 0 0
Time-to-first Pulmonary Exacerbation (PEx) - Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Timepoint [8] 0 0
From Baseline through Week 24
Secondary outcome [9] 0 0
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline - BMI was defined as weight in kg divided by height in m^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
Timepoint [9] 0 0
From Baseline at Week 24
Secondary outcome [10] 0 0
Absolute Change in Body Weight
Timepoint [10] 0 0
From Baseline at Week 24
Secondary outcome [11] 0 0
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [11] 0 0
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks)
Secondary outcome [12] 0 0
Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA
Timepoint [12] 0 0
Pre-dose on Week 4, 8, 12, and 16

Eligibility
Key inclusion criteria
Key

- Heterozygous for the F508del mutation (F/MF)

- Forced expiratory volume in 1 second (FEV1) value =40% and =90% of predicted mean for
age, sex, and height

Key
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Clinically significant cirrhosis with or without portal hypertension

- Lung infection with organisms associated with a more rapid decline in pulmonary status

- 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 3
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)
Recruitment hospital [1] 0 0
Women & Children's Hospital - North Adelaide
Recruitment hospital [2] 0 0
The Royal Children's Hospital - Parkville
Recruitment hospital [3] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [4] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- North Adelaide
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Westmead
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
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maine
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Montana
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oklahoma
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Vermont
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
United States of America
State/province [28] 0 0
West Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Wisconsin
Country [30] 0 0
Austria
State/province [30] 0 0
Graz
Country [31] 0 0
Austria
State/province [31] 0 0
Innsbruck
Country [32] 0 0
Austria
State/province [32] 0 0
Salzburg
Country [33] 0 0
Austria
State/province [33] 0 0
Vienna
Country [34] 0 0
Belgium
State/province [34] 0 0
Brussels
Country [35] 0 0
Belgium
State/province [35] 0 0
Edegem
Country [36] 0 0
Belgium
State/province [36] 0 0
Gent
Country [37] 0 0
Belgium
State/province [37] 0 0
Leuven
Country [38] 0 0
Canada
State/province [38] 0 0
British Columbia
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Canada
State/province [40] 0 0
Calgary
Country [41] 0 0
Canada
State/province [41] 0 0
Qubec
Country [42] 0 0
Canada
State/province [42] 0 0
Saint John
Country [43] 0 0
Canada
State/province [43] 0 0
Toronto
Country [44] 0 0
Canada
State/province [44] 0 0
Victoria
Country [45] 0 0
Czechia
State/province [45] 0 0
Brno
Country [46] 0 0
Czechia
State/province [46] 0 0
Praha 5
Country [47] 0 0
France
State/province [47] 0 0
Benite Cedex
Country [48] 0 0
France
State/province [48] 0 0
Bordeaux Cedex
Country [49] 0 0
France
State/province [49] 0 0
Marseille
Country [50] 0 0
France
State/province [50] 0 0
Nice
Country [51] 0 0
France
State/province [51] 0 0
Paris
Country [52] 0 0
France
State/province [52] 0 0
Rouen Cedex, Seine Maritime
Country [53] 0 0
France
State/province [53] 0 0
Suresnes
Country [54] 0 0
Germany
State/province [54] 0 0
Erlangen
Country [55] 0 0
Germany
State/province [55] 0 0
Giessen
Country [56] 0 0
Germany
State/province [56] 0 0
Hannover
Country [57] 0 0
Germany
State/province [57] 0 0
Heidelberg
Country [58] 0 0
Germany
State/province [58] 0 0
Mainz
Country [59] 0 0
Germany
State/province [59] 0 0
München
Country [60] 0 0
Germany
State/province [60] 0 0
Tuebingen
Country [61] 0 0
Germany
State/province [61] 0 0
Wuerzburg
Country [62] 0 0
Greece
State/province [62] 0 0
Maroúsi
Country [63] 0 0
Italy
State/province [63] 0 0
Ancona
Country [64] 0 0
Italy
State/province [64] 0 0
Firenze
Country [65] 0 0
Italy
State/province [65] 0 0
Genova
Country [66] 0 0
Italy
State/province [66] 0 0
Messina
Country [67] 0 0
Italy
State/province [67] 0 0
Milano
Country [68] 0 0
Italy
State/province [68] 0 0
Potenza
Country [69] 0 0
Italy
State/province [69] 0 0
Verona
Country [70] 0 0
Netherlands
State/province [70] 0 0
Amsterdam
Country [71] 0 0
Netherlands
State/province [71] 0 0
Den Haag
Country [72] 0 0
Netherlands
State/province [72] 0 0
Heidelberglaan
Country [73] 0 0
Netherlands
State/province [73] 0 0
Nijmegen
Country [74] 0 0
Netherlands
State/province [74] 0 0
Rotterdam
Country [75] 0 0
Sweden
State/province [75] 0 0
Stockholm
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Belfast
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Brimingham
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Edinburgh
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Exeter
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Leeds
Country [81] 0 0
United Kingdom
State/province [81] 0 0
London
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Manchester
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor
(TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for
F508del and a minimal function mutation (F/MF subjects).
Trial website
https://clinicaltrials.gov/show/NCT03525444
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

Summary results
Other publications