Cystic FibrosisPhase 3NCT04183790
Evaluation of Long-term Safety and Efficacy of ELX/TEZ/IVA TC Combination Therapy in Participants With Cystic Fibrosis Who Are 6 Years of Age and Older
A Phase 3 study testing ELX/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 21 sites in 5 countries.
Trial summary
The study evaluates the long-term safety, tolerability, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in participants with cystic fibrosis (CF). Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- ELX/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
- 64 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 17 Feb 2020to 24 Feb 2024
- Phase
- Phase 3
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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Completed study drug treatment in parent study (VX18-445-106 Part B, NCT03691779), or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study
Who cannot join
- History of study drug intolerance in parent study
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
21 sites in 5 countries.
21 sites in 5 countries
United States13 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Clinical Research of Charlotte
Charlotte, North Carolina, 28277
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030
The Children's Mercy Hospital
Kansas City, Missouri, 64108
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Northwell Health- Long Island Jewish Medical Center
New Hyde Park, New York, 11040
Children's Hospital of Orange County
Orange, California, 92868
Oregon Health & Science University
Portland, Oregon, 97239
Seattle Children's Hospital
Seattle, Washington, 98105
Australia2 sites
Queensland Children's Hospital
South Brisbane
The Children's Hospital at Westmead
Westmead
Canada2 sites
The Hospital for Sick Children
Toronto
British Columbia's Children's Hospital
Vancouver
Ireland2 sites
Children's Health Ireland at Crumlin
Dublin
Children's Health Ireland at Temple Street
Dublin
United Kingdom2 sites
Birmingham Children's Hospital - NHS Foundation Trust
Birmingham
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London
About this study
Official title: A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of ELX/TEZ/IVA Combination Therapy in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older
The study evaluates the long-term safety, tolerability, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in participants with cystic fibrosis (CF).
- Conditions
- Cystic Fibrosis
- Being tested
- ELX/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
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 |
|---|---|---|
| ELX/TEZ/IVA | Experimental | Participants greater than or equal to (≥) 6 years and less than (<) 12 years of age and weighing <30 kilograms (kg) received ELX (elexacaftor) 100 milligram (mg) once daily (qd) /TEZ (tezacaftor) 50 mg qd/IVA (ivacaftor) 75 mg every 12 hours (q12h) and those weighing (≥) 30 kg received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg in the treatment period for up to 192 weeks. Participants ≥12 years of age received ELX 200 mg qd/ TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for up to 192 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.
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Baseline up to Week 196
Secondary outcomes (12)
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 up to Week 192
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Measured: From Baseline up to Week 192
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.
Measured: From Baseline up to Week 192
Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kg divided by squared height in meters (m^2).
Measured: From Baseline up to Week 192
Absolute Change in BMI-for-age Z-score
BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Measured: From Baseline up to Week 192
Number of Participants With Pulmonary Exacerbations (PEx) for 106/107
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.
Measured: From Baseline up to Week 192
Number of CF-related Hospitalizations for 106/107
The total number of CF related hospitalization (Planned + Unplanned) events across all participants were reported.
Measured: From Baseline up to Week 192
Absolute Change in Lung Clearance Index 2.5 (LCI 2.5)
The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.
Measured: From Baseline up to Week 192
Absolute Change in Weight
Measured: From Baseline up to Week 192
Absolute Change in Weight-for-age Z-score
The z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Measured: From Baseline up to Week 192
Absolute Change in Height
Measured: From Baseline up to Week 192
Absolute Change in Height-for-age Z-score
The z-score is a statistical measure to describe whether a mean was above or below the standard. 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.
Measured: From Baseline up to Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2019
- Study start17 Feb 2020
- Primary completion24 Feb 2024
- Study completion24 Feb 2024
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 (4)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 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
- NCT04183790
- Sponsor's protocol ID
- VX19-445-107
- Other IDs
- 2019-001827-11, 2019
- Status last verified
- May 2025
- First submitted
- 28 Nov 2019
- Last updated
- 18 May 2025
- 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
Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ramsey B, McKone EF, Tullis E, Mall MA, Taylor-Cousar JL, Waltz D, Ahluwalia N, Chu C, Scirica CV, Davies JC. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children >/=6 Years with Cystic Fibrosis and at Least One F508del Allele: A 192-Week, Phase 3, Open-Label Extension Study. Am J Respir Crit Care Med. 2025 Oct;211(10):1915-1925. doi: 10.1164/rccm.202502-0512OC.
PubMed 40454869Heneghan 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 37983082Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ahluwalia N, Chin A, Chu C, Lu M, Menon P, Waltz D, Weinstock T, Zelazoski L, Davies JC. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial. Am J Respir Crit Care Med. 2023 Jul 1;208(1):68-78. doi: 10.1164/rccm.202301-0021OC.
PubMed 37154609Southern 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