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Cystic FibrosisPhase 3NCT03691779

Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes. Read more about this study

Who is it for?
Ages 6 to 11 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
71 participants
Where
21 sitesin 5 countries
Study dates
2 Oct 2018to 7 Aug 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 6 to 11 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% 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

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

Other trials in United States

Australia2 sites

  • Queensland Children's Hospital

    South Brisbane

  • The Children's Hospital at Westmead

    Westmead

Other trials in Australia

Canada2 sites

  • The Hospital for Sick Children

    Toronto

  • British Columbia's Children's Hospital

    Vancouver

Other trials in Canada

Ireland2 sites

  • Children's Health Ireland at Crumlin

    Dublin

  • Children's Health Ireland at Temple Street

    Dublin

Other trials in Ireland

United Kingdom2 sites

  • Birmingham Children's Hospital

    Birmingham

  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

    London

Other trials in United Kingdom

About this study

Official title: A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.

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 tablet orally once daily in the morning.

  • IVADrug

    Also called VX-770, ivacaftor

    IVA tablet orally once daily in the evening.

Study groups in NCT03691779
Study groupRoleWhat they receive
Part A: ELX/TEZ/IVAExperimentalParticipants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/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/IVAExperimentalParticipants in Part B weighing less than (<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (>=) 30 kg at Day 1 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.

  1. Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA

    Measured: Part A: Day 15

  2. Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA

    Measured: Part A: Day 15

  3. Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA

    Measured: Part A: Day 15

  4. Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)

Secondary outcomes (19)

  1. Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

    Measured: Part A: Day 15

  2. Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

    Measured: Part A: Day 15

  3. Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)

    Measured: Part A: Day 15

  4. Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)

    The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.

    Measured: Part A: Day 15

  5. Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs

    Measured: Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)

  6. Part B: 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: Part B: From Baseline Through Week 24

  7. Part B: Absolute Change in Sweat Chloride (SwCl)

    Sweat samples were collected using an approved collection device.

    Measured: Part B: From Baseline Through Week 24

  8. Part B: 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: Part B: From Baseline Through Week 24

  9. Part B: Absolute Change in Body Mass Index (BMI)

    BMI was defined as weight in kg divided by squared height in meters (m^2).

    Measured: Part B: From Baseline at Week 24

  10. Part B: 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 value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

    Measured: Part B: From Baseline at Week 24

  11. Part B: Absolute Change in Weight

    Measured: Part B: From Baseline at Week 24

  12. Part B: Absolute Change in Weight-for-age Z-Score

    The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

    Measured: Part B: From Baseline at Week 24

  13. Part B: Absolute Change in Height

    Measured: Part B: From Baseline at Week 24

  14. Part B: Absolute Change in Height-for-Age Z-Score

    The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

    Measured: Part B: From Baseline at Week 24

  15. Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale

    The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.

    Measured: Part B: At Week 24

  16. Part B: Number of Pulmonary Exacerbations Events

    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.

    Measured: Part B: From Baseline Through Week 24

  17. Part B: Number of CF Related Hospitalizations

    The total number of CF related hospitalization events across all participants were reported.

    Measured: Part B: From Baseline Through Week 24

  18. Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)

    Measured: Part B: At Week 4

  19. Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)

    LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

    Measured: Part B: 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.

  1. First posted2 Oct 2018
  2. Study start2 Oct 2018
  3. Primary completion7 Aug 2020
  4. Study completion7 Aug 2020

Resources

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
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03691779
Sponsor's protocol ID
VX18-445-106
Other IDs
2018-001695-38, 2018
Status last verified
Aug 2021
First submitted
28 Sep 2018
Last updated
22 Oct 2021
FDA-regulated drug
Yes
FDA-regulated device
No
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 37983082

  • Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA. A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2021 Jun 15;203(12):1522-1532. doi: 10.1164/rccm.202102-0509OC.

    PubMed 33734030

  • 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. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

    PubMed 33331662

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 21 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 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 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Australia, Canada, Ireland, 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 22 Oct 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?

Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA (time frame: Part A: Day 15). The study lists 4 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 NCT03691779, 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 22 Oct 2021.

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