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Cystic FibrosisPhase 3NCT02953314

A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)

A Phase 3 study testing TEZ, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 33 sites in 2 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 is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the pharmacokinetic (PK), safety, and tolerability of multiple doses of tezacaftor (TEZ) in combination with ivacaftor (IVA) in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del- CF… 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?
TEZ, 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
33 sitesin 2 countries
Study dates
Nov 2016to Sep 2018
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

  • Subjects who weigh ≥15 kg without shoes at the Screening Visit.
  • All genotypes as specified by the study protocol are eligible in Part A.
  • The following genotypes are eligible in Part B:
  • homozygous for the F508del CFTR mutation
  • heterozygous for the F508del CFTR mutation and with a second allele with a CFTR mutation predicted to have residual function.
  • heterozygous for the F508del CFTR mutation and with a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
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  • Subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L or chronic sinopulmonary and/or gastrointestinal disease consistent with a diagnosis of CF. Subjects who are homozygous for the F508del-CFTR mutation must have a sweat chloride value ≥60 mmol/L.
  • Subjects with ppFEV1 of ≥40 percentage points at the Screening Visit
  • Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
  • Subjects who are willing to remain on their stable CF medication regimen through Day 14 (Part A) or through Week 24 (Part B) or, if applicable, through the Safety Follow up Visit.
  • Subjects who are able to swallow tablets.
  • Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Day 1 Visit before receiving the first dose of study drug.
  • Subjects of childbearing potential who are sexually active must meet the contraception requirements

Who cannot join

  • History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
  • Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1
  • Colonization with organisms associated with a more rapid decline in pulmonary status.
  • A standard 12 lead ECG demonstrating QTc >450 msec at the Screening Visit.
  • History of solid organ or hematological transplantation at the Screening Visit.
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  • Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator (except physician-prescribed Kalydeco for approved indications) within 30 days of screening.
  • Use of restricted medication or food within a specified duration before the Screening Visit or first dose of study drug and/or unwillingness to maintain the restrictions.
  • History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination at the Screening Visit.
  • Pregnant and nursing females.

Trial locations and contacts

33 sites in 2 countries.

33 sites in 2 countries

United States30 sites
  • Study site

    Anchorage, Alaska

  • Study site

    Atlanta, Georgia

  • Study site

    Aurora, Colorado

  • Study site

    Austin, Texas

  • Study site

    Birmingham, Alabama

  • Study site

    Boise, Idaho

  • Study site

    Boston, Massachusetts

  • Study site

    Buffalo, New York

  • Study site

    Charleston, South Carolina

  • Study site

    Cleveland, Ohio

  • Study site

    Fort Worth, Texas

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Kansas City, Missouri

  • Study site

    Little Rock, Arkansas

  • Study site

    Los Angeles, California

  • Study site

    Manchester, New Hampshire

  • Study site

    Milwaukee, Wisconsin

  • Study site

    Minneapolis, Minnesota

  • Study site

    New York, New York

  • Study site

    Norfolk, Virginia

  • Study site

    Orlando, Florida

  • Study site

    Palo Alto, California

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Seattle, Washington

  • Study site

    Sioux Falls, South Dakota

  • Study site

    St. Petersburg, Florida

  • Study site

    Syracuse, New York

  • Study site

    Wilmington, Delaware

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

Canada3 sites
  • Study site

    Montreal, Quebec

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

Other trials in Canada

About this study

Official title: A Phase 3, Open Label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661 in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutation

This is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the pharmacokinetic (PK), safety, and tolerability of multiple doses of tezacaftor (TEZ) in combination with ivacaftor (IVA) in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del- CF transmembrane conductance regulator protein (CFTR) mutation.

Conditions
Cystic Fibrosis
Being tested
TEZ, 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.

  • TEZDrug

    Also called tezacaftor, VX-661

  • TEZ/IVADrug

    Also called tezacaftor/ivacaftor, VX-661/VX-770

  • IVADrug

    Also called ivacaftor, VX-770

Study groups in NCT02953314
Study groupRoleWhat they receive
Part AExperimentalParticipants weighing <25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days. Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days.
Receives: Drug: TEZ; Drug: IVA
Part BExperimentalParticipants weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks. Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks.
Receives: Drug: 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 Concentration (Cmax) of TEZ and IVA

    Measured: Day 1 and Day 14

  2. Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA

    Measured: Day 1 and Day 14

  3. Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Day 1 up to Week 28

Secondary outcomes (16)
  1. Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

    Measured: Day 1 and Day 14

  2. Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

    Measured: Day 1 and Day 14

  3. Part A: Number of Participants With AEs and SAEs

    Measured: Day 1 up to Day 28

  4. Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA)

    Measured: Week 16

  5. Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA )

    Measured: Week 16

  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: From Baseline through Week 24

  7. Part B: Relative Change in 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

  8. Part B: Absolute Change in Weight

    Measured: From Baseline at Week 24

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

    z-score is a statistical measure to describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score. 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. Higher values are indicative of higher weight.

    Measured: From Baseline at Week 24

  10. Part B: Absolute Change in Height

    Measured: From Baseline at Week 24

  11. Part B: Absolute Change in Height-for-age z-Score

    z-score is a statistical measure to describe whether a mean was above or below the standard. Height, adjusted for age and sex, was analyzed as height-for-age z-score. 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. Higher values are indicative of higher height.

    Measured: From Baseline at Week 24

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

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

    Measured: From Baseline at Week 24

  13. Part B: Absolute Change in BMI-for-age z-Score

    BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. 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. Higher values are indicative of higher BMI.

    Measured: From Baseline at Week 24

  14. Part B: Absolute Change in Sweat Chloride

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline through Week 4

  15. Part B: Absolute Change in Sweat Chloride

    Sweat samples were collected using an approved collection device.

    Measured: From Baseline through Week 24

  16. 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: 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 Nov 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionSep 2018
  4. Study completionSep 2018

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
Parallel groups
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02953314
Sponsor's protocol ID
VX15-661-113
Other IDs
2017-001164-38, 2017
Status last verified
Feb 2020
First submitted
18 Oct 2016
Last updated
4 Mar 2020
Data monitoring committee
Yes

Publications

  • Walker S, Flume P, McNamara J, Solomon M, Chilvers M, Chmiel J, Harris RS, Haseltine E, Stiles D, Li C, Ahluwalia N, Zhou H, Owen CA, Sawicki G; VX15-661-113 Investigator Group. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):708-713. doi: 10.1016/j.jcf.2019.06.009. Epub 2019 Jun 26.

    PubMed 31253540

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TEZ, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 33 sites in 2 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 13 inclusion and 10 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 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Canada. 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 5 Dec 2019). 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 Concentration (Cmax) of TEZ and IVA (time frame: Day 1 and Day 14). 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 NCT02953314, which also lists 1 linked publication.

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 4 Mar 2020.

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