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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02516410




Registration number
NCT02516410
Ethics application status
Date submitted
28/07/2015
Date registered
5/08/2015
Date last updated
12/06/2018

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
Secondary ID [1] 0 0
2014-004787-37
Secondary ID [2] 0 0
VX14-661-107
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
Experimental: VX-661/IVA - VX-661 100 milligram (mg) plus IVA 150 mg fixed dose combination (FDC) tablet administered orally in the morning and IVA 150 mg film-coated tablet administered orally in the evening up to Week 12.

Placebo comparator: Placebo - Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA film-coated tablet administered orally in the evening up to Week 12.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12
Timepoint [1] 0 0
Baseline, Through Week 12
Secondary outcome [1] 0 0
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12
Timepoint [1] 0 0
Baseline, Through Week 12
Secondary outcome [2] 0 0
Number of Pulmonary Exacerbation Events
Timepoint [2] 0 0
Baseline through Week 12
Secondary outcome [3] 0 0
Number of Pulmonary Exacerbation Events Per Year
Timepoint [3] 0 0
Baseline through Week 12
Secondary outcome [4] 0 0
Absolute Change From Baseline in Body Mass Index (BMI) at Week 12
Timepoint [4] 0 0
Baseline, Week 12
Secondary outcome [5] 0 0
Relative Change From Baseline in Percent Predicted FEV1 Through Week 12
Timepoint [5] 0 0
Baseline, Through Week 12
Secondary outcome [6] 0 0
Absolute Change From Baseline in Sweat Chloride Through Week 12
Timepoint [6] 0 0
Baseline, Through Week 12
Secondary outcome [7] 0 0
Number of Participants With at Least One Pulmonary Exacerbation Through Week 12
Timepoint [7] 0 0
Baseline through Week 12
Secondary outcome [8] 0 0
Absolute Change From Baseline in BMI Z-score at Week 12 (in Participants Less Than [<] 20 Years Old at the Time of Screening)
Timepoint [8] 0 0
Baseline, Week 12
Secondary outcome [9] 0 0
Absolute Change From Baseline in Body Weight at Week 12
Timepoint [9] 0 0
Baseline, Week 12
Secondary outcome [10] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [10] 0 0
Baseline up to Week 16
Secondary outcome [11] 0 0
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolite (M1 VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
Timepoint [11] 0 0
Pre-morning dose on Week 2, Week 4, Week 8 and Week 12

Eligibility
Key inclusion criteria
* Confirmed diagnosis of CF defined as a sweat chloride value greater than or equal to (>=)60 millimole per liter (mmol/L) by quantitative pilocarpine iontophoresis.
* Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.
* Forced Expiratory Volume in 1 Second (FEV1) >=40 percent (%) and less than or equal to (<=)90% of predicted normal for age, sex, and height at Screening Visit.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
* History of solid organ or hematological transplantation.
* Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator within 30 days of screening.
* Pregnant or nursing females.

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 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
1/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/06/2016
Sample size
Target
Accrual to date
Final
168
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
- Brisban
Recruitment hospital [2] 0 0
- Chermside
Recruitment hospital [3] 0 0
- Herston
Recruitment hospital [4] 0 0
- Innsbruck
Recruitment hospital [5] 0 0
- Westmead
Recruitment postcode(s) [1] 0 0
- Brisban
Recruitment postcode(s) [2] 0 0
- Chermside
Recruitment postcode(s) [3] 0 0
- Herston
Recruitment postcode(s) [4] 0 0
- Innsbruck
Recruitment postcode(s) [5] 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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
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
Virginia
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Austria
State/province [19] 0 0
Graz
Country [20] 0 0
Austria
State/province [20] 0 0
Innsbruck
Country [21] 0 0
Austria
State/province [21] 0 0
Salzburg
Country [22] 0 0
Canada
State/province [22] 0 0
British Columbia
Country [23] 0 0
Canada
State/province [23] 0 0
Montreal
Country [24] 0 0
France
State/province [24] 0 0
Bron Cedex
Country [25] 0 0
France
State/province [25] 0 0
Montpellier Cedex 5
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 14
Country [27] 0 0
France
State/province [27] 0 0
Paris Cedex 19
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
Israel
State/province [29] 0 0
Haifa
Country [30] 0 0
Israel
State/province [30] 0 0
Hashomer
Country [31] 0 0
Israel
State/province [31] 0 0
Jerusalem
Country [32] 0 0
Israel
State/province [32] 0 0
Petah Tikva
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Valencia

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

Ethics approval
Ethics application status

Summary
Brief summary
Study to evaluate the efficacy of VX-661 in combination with ivacaftor (IVA, VX-770) through Week 12 in participants with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or IVA therapy (F508del/not responsive \[NR\]).
Trial website
https://clinicaltrials.gov/study/NCT02516410
Trial related presentations / publications
Munck A, Kerem E, Ellemunter H, Campbell D, Wang LT, Ahluwalia N, Owen CA, Wainwright C. Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations. J Cyst Fibros. 2020 Nov;19(6):962-968. doi: 10.1016/j.jcf.2020.04.015. Epub 2020 Jun 13.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02516410