Cystic FibrosisPhase 3NCT04537793
Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years
A Phase 3 study testing ELX/TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 22 sites in 5 countries.
Trial summary
This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age. Read more about this study
- Who is it for?
- Ages 2 to 5 years
- 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
- 83 participants
- Where
- 22 sitesin 5 countries
- Study dates
- 19 Nov 2020to 3 Jun 2022
- 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 2 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Homozygous for the F508del mutation or heterozygous for F508del and a minimal function (MF) mutation (F/F or F/MF genotypes)
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
22 sites in 5 countries.
22 sites in 5 countries
United States13 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
NC TraCS Institute - CTRC University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
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
Stanford University
Palo Alto, California, 94304
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University
Portland, Oregon, 97239
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine / St. Louis Children's Hospital
St Louis, Missouri, 63110
Banner University of Arizona Medical Center
Tucson, Arizona, 85724
Australia3 sites
Telethon Kids Institute
Nedlands
The Royal Children's Hospital
Parkville, VIC
Queensland Children's Hospital
South Brisbane
Canada2 sites
The Hospital for Sick Children
Toronto
British Columbia Children's Hospital
Vancouver
Germany2 sites
Charite Paediatric Pulmonology Department
Berlin
Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie
Essen
United Kingdom2 sites
Alder Hey Children's NHS Foundation Trust
Liverpool
Royal Brompton Hospital
London
About this study
Official title: A Phase 3 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 2 Through 5 Years of Age
This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.
- 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 granules for oral administration.
IVADrug
Also called VX-770, ivacaftor
Granules for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Part A: ELX/TEZ/IVA | Experimental | Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. Receives: Drug: ELX/TEZ/IVA; Drug: IVA |
| Part B: ELX/TEZ/IVA | Experimental | Participants weighing (>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (>=)10 kg to less than (<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) 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.
Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites
Measured: From Day 1 through Day 15
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 up to Day 43
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 up to Week 28
Secondary outcomes (3)
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites
Measured: From Day 1 through Week 16
Part B: Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Measured: From Baseline through Week 24
Part B: 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 through Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start19 Nov 2020
- Primary completion3 Jun 2022
- Study completion3 Jun 2022
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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 83 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
- NCT04537793
- Sponsor's protocol ID
- VX20-445-111
- Other IDs
- 2020-002251-38
- Status last verified
- Jun 2023
- First submitted
- 28 Aug 2020
- Last updated
- 28 Jun 2023
- 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
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 37983082Goralski JL, Hoppe JE, Mall MA, McColley SA, McKone E, Ramsey B, Rayment JH, Robinson P, Stehling F, Taylor-Cousar JL, Tullis E, Ahluwalia N, Chin A, Chu C, Lu M, Niu T, Weinstock T, Ratjen F, Rosenfeld M. Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2023 Jul 1;208(1):59-67. doi: 10.1164/rccm.202301-0084OC.
PubMed 36921081Southern 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 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 2 Through 5 Years of Age
- ClinicalTrials.gov ID
- NCT04537793
- Acronym / sponsor ID
- VX20-445-111
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- 3 Jun 2022 (actual)
- Study completion
- 3 Jun 2022 (actual)
- First posted
- 3 Sep 2020 (actual)
- Results
- Posted 28 Jun 2023
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 safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: ELX/TEZ/IVA | Experimental | Drug: ELX/TEZ/IVA, Drug: IVAParticipants weighing greater than or equal to (>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. |
| Part B: ELX/TEZ/IVA | Experimental | Drug: ELX/TEZ/IVA, Drug: IVAParticipants weighing (>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (>=)10 kg to less than (<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks. |
Who may qualify
- Ages
- 2 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Homozygous for the F508del mutation or heterozygous for F508del and a minimal function (MF) mutation (F/F or F/MF genotypes)
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/ivacaftorFixed dose combination granules for oral administration. | Drug | Part A: ELX/TEZ/IVA, Part B: ELX/TEZ/IVA |
| IVAAlso: VX-770, ivacaftorGranules for oral administration. | Drug | Part A: ELX/TEZ/IVA, Part B: ELX/TEZ/IVA |
Primary outcome
Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites
Time frame: From Day 1 through Day 15
Part A: 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 up to Day 43
Part B: 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 up to Week 28
3 secondary outcomes
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites
Time frame: From Day 1 through Week 16
Part B: Absolute Change in Sweat Chloride (SwCl)
Time frame: From Baseline through Week 24
Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5)
Time frame: From Baseline through Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
- 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 36921081Goralski JL, Hoppe JE, Mall MA, McColley SA, McKone E, Ramsey B, Rayment JH, Robinson P, Stehling F, Taylor-Cousar JL, Tullis E, Ahluwalia N, Chin A, Chu C, Lu M, Niu T, Weinstock T, Ratjen F, Rosenfeld M. Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2023 Jul 1;208(1):59-67. doi: 10.1164/rccm.202301-0084OC.
- 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.
22 sites in 5 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 and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 22 sites in 5 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 1 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 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Australia, Canada, Germany, United Kingdom. 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 28 Jun 2023). 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?
Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites (time frame: From Day 1 through Day 15). The study lists 3 primary outcomes in all. 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 NCT04537793, 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 28 Jun 2023.