Clinical trial NCT02953314: A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2016-11-02
Enrollment: 83
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA
timeFrame: Day 1 and Day 14
measure: Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA
timeFrame: Day 1 and Day 14
measure: Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 28
Secondary outcomes:
measure: Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)
timeFrame: Day 1 and Day 14
measure: Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)
timeFrame: Day 1 and Day 14
measure: Part A: Number of Participants With AEs and SAEs
timeFrame: Day 1 up to Day 28
measure: Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA)
timeFrame: Week 16
measure: Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA )
timeFrame: Week 16
measure: Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: From Baseline through Week 24
measure: Part B: Relative Change in ppFEV1
timeFrame: From Baseline through Week 24
measure: Part B: Absolute Change in Weight
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Weight-for-age Z-Score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Height
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Height-for-age z-Score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Body Mass Index (BMI)
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in BMI-for-age z-Score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Sweat Chloride
timeFrame: From Baseline through Week 4
measure: Part B: Absolute Change in Sweat Chloride
timeFrame: From Baseline through Week 24
measure: Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
timeFrame: From Baseline through Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Anchorage
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state: Alaska
city: Little Rock
country: United States
state: Arkansas
city: Los Angeles
country: United States
state: California
city: Palo Alto
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state: California
city: Aurora
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state: Colorado
city: Wilmington
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state: Delaware
city: Orlando
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state: Florida
city: Saint Petersburg
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state: Florida
city: Atlanta
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state: Georgia
city: Boise
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state: Idaho
city: Indianapolis
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state: Indiana
city: Boston
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state: Massachusetts
city: Minneapolis
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state: Minnesota
city: Kansas City
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state: Missouri
city: Manchester
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state: New Hampshire
city: Buffalo
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state: New York
city: New York
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state: New York
city: Syracuse
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state: New York
city: Winston-Salem
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state: North Carolina
city: Cleveland
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state: Ohio
city: Pittsburgh
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state: Pennsylvania
city: Charleston
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state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Austin
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state: Texas
city: Fort Worth
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state: Texas
city: Houston
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state: Texas
city: Norfolk
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state: Virginia
city: Seattle
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state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montréal
country: Canada
state: Quebec
Study officials:
References:
citation: 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.