Cystic FibrosisPhase 3NCT04105972
A Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
A Phase 3 study testing ELX/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 35 sites in 4 countries.
Trial summary
This study will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- ELX/TEZ/IVA, TEZ/IVA and IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 35 sitesin 4 countries
- Study dates
- 3 Oct 2019to 24 Jul 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Homozygous for the F508del mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Who cannot join
- 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
Trial locations and contacts
35 sites in 4 countries.
35 sites in 4 countries
United Kingdom17 sites
Belfast City Hospital
Belfast
University Hospitals Birmingham NHS Foundation Trust
Birmingham
University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital
Bristol
Papworth Hospital NHS Foundation Trust, Papworth Everard
Cambridge
Western General Hospital
Edinburgh
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter
Clinical Research Facility, Queen Elizabeth University Hospital
Glasgow
St. James University Hospital
Leeds
Leeds General Infirmary
Leeds, West Yorkshire
Alder Hey Children's Alder Hey Children's NHS Foundation Trust
Liverpool
Great Ormond Street Hospital for Sick Children
London
London and St Bartholomew's Hospital
London
The University Hospital of South Manchester
Manchester
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Newcastle upon Tyne
Nottingham University Hospitals NHS Trust, Queens Medical Center
Nottingham
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
Penarth
Southampton General Hospital
Southampton
Germany8 sites
Charite Paediatric Pulmonology Department
Berlin
Universitaetsklinkum Koeln, CF-Studienzentrum
Cologne
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen
Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
Essen
Johann Wolfgang Goethe University
Frankfurt
Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
Jena
Klinikum Innenstadt, University of Munich
München
Pneumologisches Studienzentrum Muenchen-West
München
Australia6 sites
The Prince Charles Hospital
Chermside
Institute for Respiratory Health
Nedlands
Perth Children's Hospital
Nedlands
John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
New Lambton
The Royal Children's Hospital
Parkville, VIC
Queensland Children's Hospital
South Brisbane
Belgium4 sites
Universitair Ziekenhuis Brussel - Campus Jette
Brussels
UZ Antwerpen
Edegem
Universitair Ziekenhuis Gent
Ghent
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
About this study
Official title: A Phase 3b, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
This study will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del.
- Conditions
- Cystic Fibrosis
- Being tested
- ELX/TEZ/IVA, TEZ/IVA, IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ELX/TEZ/IVADrug
Also called VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor
FDC tablet for oral administration.
TEZ/IVADrug
Also called VX-661/VX-770, tezacaftor/ivacaftor
Fixed-dose combination (FDC) tablet for oral administration.
IVADrug
Also called VX-770, ivacaftor
Mono tablet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| TEZ/IVA | Active comparator | Following TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks. Receives: Drug: TEZ/IVA; Drug: IVA |
| ELX/TEZ/IVA | Experimental | Following 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 24 weeks. Receives: Drug: ELX/TEZ/IVA; Drug: IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change in CF 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.
Measured: From Baseline Through Week 24
Secondary outcomes (3)
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.
Measured: From Baseline Through Week 24
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Measured: From Baseline Through Week 24
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 in the 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 Week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start3 Oct 2019
- Primary completion24 Jul 2020
- Study completion24 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04105972
- Sponsor's protocol ID
- VX18-445-109
- Other IDs
- 2019-001735-31, 2019
- Status last verified
- Jul 2021
- First submitted
- 24 Sep 2019
- Last updated
- 18 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
- Expanded access
- Available
Publications
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PubMed 37983082Sutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, Van Braeckel E, Wainwright CE, Watson D, Ahluwalia N, Bruinsma BG, Harris C, Lam AP, Lou Y, Moskowitz SM, Tian S, Yuan J, Waltz D, Mall MA; VX18-445-109 study group. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022 Mar;10(3):267-277. doi: 10.1016/S2213-2600(21)00454-9. Epub 2021 Dec 20.
PubMed 34942085Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PubMed 33331662
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects, Homozygous for F508del
- ClinicalTrials.gov ID
- NCT04105972
- Acronym / sponsor ID
- VX18-445-109
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 3 Oct 2019 (actual)
- Primary completion
- 24 Jul 2020 (actual)
- Study completion
- 24 Jul 2020 (actual)
- First posted
- 26 Sep 2019 (actual)
- Results
- Posted 18 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy, safety, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for F508del.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEZ/IVA | Active comparator | Drug: TEZ/IVA, Drug: IVAFollowing TEZ/IVA run-in period of 4 weeks, participants received TEZ 100 milligrams (mg) once daily (qd)/IVA 150 mg every 12 hours (q12h) in the treatment period for 24 weeks. |
| ELX/TEZ/IVA | Experimental | Drug: ELX/TEZ/IVA, Drug: IVAFollowing 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 24 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Homozygous for the F508del mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ELX/TEZ/IVAAlso: VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftorFDC tablet for oral administration. | Drug | ELX/TEZ/IVA |
| TEZ/IVAAlso: VX-661/VX-770, tezacaftor/ivacaftorFixed-dose combination (FDC) tablet for oral administration. | Drug | TEZ/IVA |
| IVAAlso: VX-770, ivacaftorMono tablet for oral administration. | Drug | ELX/TEZ/IVA, TEZ/IVA |
Primary outcome
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline Through Week 24
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.
3 secondary outcomes
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline Through Week 24
Absolute Change in Sweat Chloride (SwCl)
Time frame: From Baseline Through Week 24
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 in the 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 Week 28)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37983082Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
- Derived from this study: PubMed 34942085Sutharsan S, McKone EF, Downey DG, Duckers J, MacGregor G, Tullis E, Van Braeckel E, Wainwright CE, Watson D, Ahluwalia N, Bruinsma BG, Harris C, Lam AP, Lou Y, Moskowitz SM, Tian S, Yuan J, Waltz D, Mall MA; VX18-445-109 study group. Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. Lancet Respir Med. 2022 Mar;10(3):267-277. doi: 10.1016/S2213-2600(21)00454-9. Epub 2021 Dec 20.
- Derived from this study: PubMed 33331662Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ELX/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 35 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United Kingdom, Germany, Australia, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score (time frame: From Baseline Through Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04105972, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2021.