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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02953314
Recruitment Status : Completed
First Posted : November 2, 2016
Results First Posted : December 5, 2019
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
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Brief 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 transmembrane conductance regulator protein (CFTR) mutation.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: TEZ Drug: TEZ/IVA Drug: IVA Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 2016
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A

Participants 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.

 Drug: TEZ
Other Names:
  • tezacaftor
  • VX-661

Drug: IVA
Other Names:
  • ivacaftor
  • VX-770
Experimental: Part B

Participants 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.

 Drug: TEZ/IVA
Other Names:
  • tezacaftor/ivacaftor
  • VX-661/VX-770

Drug: IVA
Other Names:
  • ivacaftor
  • VX-770


Outcome Measures
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Primary Outcome Measures :
  1. Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA [ Time Frame: Day 1 and Day 14 ]
  2. Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA [ Time Frame: Day 1 and Day 14 ]
  3. Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]

Secondary Outcome Measures :
  1. Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [ Time Frame: Day 1 and Day 14 ]
  2. Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [ Time Frame: Day 1 and Day 14 ]
  3. Part A: Number of Participants With AEs and SAEs [ Time Frame: 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) [ Time Frame: Week 16 ]
  5. Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA ) [ Time Frame: Week 16 ]
  6. Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  7. Part B: Relative Change in ppFEV1 [ Time Frame: From Baseline through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  8. Part B: Absolute Change in Weight [ Time Frame: From Baseline at Week 24 ]
  9. Part B: Absolute Change in Weight-for-age Z-Score [ Time Frame: From Baseline at Week 24 ]
    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.

  10. Part B: Absolute Change in Height [ Time Frame: From Baseline at Week 24 ]
  11. Part B: Absolute Change in Height-for-age z-Score [ Time Frame: From Baseline at Week 24 ]
    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.

  12. Part B: Absolute Change in Body Mass Index (BMI) [ Time Frame: From Baseline at Week 24 ]
    BMI was defined as weight in kg divided by height in square meter (m^2).

  13. Part B: Absolute Change in BMI-for-age z-Score [ Time Frame: From Baseline at Week 24 ]
    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.

  14. Part B: Absolute Change in Sweat Chloride [ Time Frame: From Baseline through Week 4 ]
    Sweat samples were collected using an approved collection device.

  15. Part B: Absolute Change in Sweat Chloride [ Time Frame: From Baseline through Week 24 ]
    Sweat samples were collected using an approved collection device.

  16. Part B: Absolute Change in Cystic Fibrosis 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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.
  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953314


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, Alaska
Anchorage, Alaska, United States
United States, Arkansas
Little Rock, Arkansas, United States
United States, California
Los Angeles, California, United States
Palo Alto, California, United States
United States, Colorado
Aurora, Colorado, United States
United States, Delaware
Wilmington, Delaware, United States
United States, Florida
Orlando, Florida, United States
Saint Petersburg, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Idaho
Boise, Idaho, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Minneapolis, Minnesota, United States
United States, Missouri
Kansas City, Missouri, United States
United States, New Hampshire
Manchester, New Hampshire, United States
United States, New York
Buffalo, New York, United States
New York, New York, United States
Syracuse, New York, United States
United States, North Carolina
Winston-Salem, North Carolina, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, South Dakota
Sioux Falls, South Dakota, United States
United States, Texas
Austin, Texas, United States
Fort Worth, Texas, United States
Houston, Texas, United States
United States, Virginia
Norfolk, Virginia, United States
United States, Washington
Seattle, Washington, United States
United States, Wisconsin
Milwaukee, Wisconsin, United States
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montréal, Quebec, Canada
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] July 19, 2017
Statistical Analysis Plan  [PDF] June 22, 2018

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02953314    
Other Study ID Numbers: VX15-661-113
2017-001164-38 ( EudraCT Number )
First Posted: November 2, 2016    Key Record Dates
Results First Posted: December 5, 2019
Last Update Posted: March 4, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action