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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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)
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)
Timepoint [1] 0 0
From Baseline through Week 24
Secondary outcome [2] 0 0
Number of Pulmonary Exacerbations (PEx)
Timepoint [2] 0 0
From Baseline through Week 24
Secondary outcome [3] 0 0
Absolute Change in Sweat Chloride (SwCl)
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
Timepoint [4] 0 0
From Baseline through Week 24
Secondary outcome [5] 0 0
Absolute Change in Body Mass Index (BMI)
Timepoint [5] 0 0
From Baseline at Week 24
Secondary outcome [6] 0 0
Absolute Change in Sweat Chloride
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
Timepoint [7] 0 0
From Baseline at Week 4
Secondary outcome [8] 0 0
Time-to-first Pulmonary Exacerbation (PEx)
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
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
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
15/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/04/2019
Sample size
Target
Accrual to date
Final
405
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
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Graz
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Greece
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Ancona
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Firenze
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Genova
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Messina
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Potenza
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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/study/NCT03525444
Trial related presentations / publications
Middleton PG, Mall MA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R; VX17-445-102 Study Group. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov 7;381(19):1809-1819. doi: 10.1056/NEJMoa1908639. Epub 2019 Oct 31.
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
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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/NCT03525444