Register a trial

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

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/study/NCT04058353




Registration number
NCT04058353
Ethics application status
Date submitted
14/08/2019
Date registered
15/08/2019

Titles & IDs
Public title
A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
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 Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Secondary ID [1] 0 0
2018-002835-76
Secondary ID [2] 0 0
VX18-445-104
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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ELX/TEZ/IVA
Treatment: Drugs - IVA
Treatment: Drugs - TEZ/IVA

Active comparator: Control: IVA or TEZ/IVA - Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.

Experimental: TC: ELX/TEZ/IVA - Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.


Treatment: Drugs: ELX/TEZ/IVA
FDC tablet for oral administration.

Treatment: Drugs: IVA
Mono-tablet for oral administration.

Treatment: Drugs: TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
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) for ELX/TEZ/IVA Group
Timepoint [1] 0 0
From Baseline Through Week 8
Secondary outcome [1] 0 0
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group
Timepoint [1] 0 0
From Baseline Through Week 8
Secondary outcome [2] 0 0
Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group
Timepoint [2] 0 0
From Baseline Through Week 8
Secondary outcome [3] 0 0
Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group
Timepoint [3] 0 0
From Baseline Through Week 8
Secondary outcome [4] 0 0
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group
Timepoint [4] 0 0
From Baseline Through Week 8
Secondary outcome [5] 0 0
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group
Timepoint [5] 0 0
From Baseline Through Week 8
Secondary outcome [6] 0 0
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
Day 1 up to Week 12

Eligibility
Key inclusion criteria
Key

* Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
* 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
Sex
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
28/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/06/2020
Sample size
Target
Accrual to date
Final
271
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne, VIC
Recruitment hospital [3] 0 0
Perth Children's Hospital - Nedlands
Recruitment hospital [4] 0 0
The Royal Children's Hospital - Parkville, VIC
Recruitment hospital [5] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Chermside
Recruitment postcode(s) [2] 0 0
- Melbourne, VIC
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment postcode(s) [4] 0 0
- Parkville, VIC
Recruitment postcode(s) [5] 0 0
- South Brisbane
Recruitment postcode(s) [6] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
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
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
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
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
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
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New Hampshire
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Oregon
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Belgium
State/province [25] 0 0
Brussels
Country [26] 0 0
Belgium
State/province [26] 0 0
Gent
Country [27] 0 0
Belgium
State/province [27] 0 0
Leuven
Country [28] 0 0
Canada
State/province [28] 0 0
Edmonton
Country [29] 0 0
Canada
State/province [29] 0 0
Québec
Country [30] 0 0
Canada
State/province [30] 0 0
Toronto
Country [31] 0 0
Canada
State/province [31] 0 0
Vancouver
Country [32] 0 0
Denmark
State/province [32] 0 0
Copenhagen
Country [33] 0 0
France
State/province [33] 0 0
Benite Cedex
Country [34] 0 0
France
State/province [34] 0 0
Bordeaux cedex
Country [35] 0 0
France
State/province [35] 0 0
Lille
Country [36] 0 0
France
State/province [36] 0 0
Marseille
Country [37] 0 0
France
State/province [37] 0 0
Montpellier Cedex 5
Country [38] 0 0
France
State/province [38] 0 0
Paris Cedex 15
Country [39] 0 0
France
State/province [39] 0 0
Paris
Country [40] 0 0
France
State/province [40] 0 0
Rennes Cedex
Country [41] 0 0
Germany
State/province [41] 0 0
Berlin
Country [42] 0 0
Germany
State/province [42] 0 0
Erlangen
Country [43] 0 0
Germany
State/province [43] 0 0
Essen
Country [44] 0 0
Germany
State/province [44] 0 0
Giessen
Country [45] 0 0
Germany
State/province [45] 0 0
Halle
Country [46] 0 0
Germany
State/province [46] 0 0
Muenchen
Country [47] 0 0
Germany
State/province [47] 0 0
Würzburg
Country [48] 0 0
Ireland
State/province [48] 0 0
Cork
Country [49] 0 0
Ireland
State/province [49] 0 0
Dublin
Country [50] 0 0
Israel
State/province [50] 0 0
Limerick
Country [51] 0 0
Italy
State/province [51] 0 0
Ancona
Country [52] 0 0
Italy
State/province [52] 0 0
Genova
Country [53] 0 0
Italy
State/province [53] 0 0
Milano
Country [54] 0 0
Italy
State/province [54] 0 0
Orbassano
Country [55] 0 0
Italy
State/province [55] 0 0
Rome
Country [56] 0 0
Italy
State/province [56] 0 0
Verona
Country [57] 0 0
Netherlands
State/province [57] 0 0
Den Haag
Country [58] 0 0
Netherlands
State/province [58] 0 0
Heidelberglaan
Country [59] 0 0
Netherlands
State/province [59] 0 0
Nijmegen
Country [60] 0 0
Spain
State/province [60] 0 0
Barcelona
Country [61] 0 0
Spain
State/province [61] 0 0
Murcia
Country [62] 0 0
Spain
State/province [62] 0 0
Sevilla
Country [63] 0 0
Spain
State/province [63] 0 0
Valencia
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Cambridge
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Exeter
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Glasgow
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Leeds
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Liverpool
Country [69] 0 0
United Kingdom
State/province [69] 0 0
London
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Manchester
Country [71] 0 0
United Kingdom
State/province [71] 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
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent research/clinical-trial-data-sharing


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04058353