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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02953314
• Date of registration: 18/10/2016
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)
• Scientific 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
• Date of first enrolment: November 2016
• Target sample size: 83
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02953314
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, United States

Key inclusion & exclusion 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.



Age minimum: 6 Years
Age maximum: 11 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: IVA

Drug: TEZ/IVA

Drug: TEZ

Primary Outcome(s)

Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA [Time Frame: Day 1 and Day 14]

Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA [Time Frame: Day 1 and Day 14]

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(s)

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

Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [Time Frame: From Baseline through Week 24]

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

Part B: Relative Change in ppFEV1 [Time Frame: From Baseline through Week 24]

Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [Time Frame: From Baseline through Week 24]

Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA ) [Time Frame: Week 16]

Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [Time Frame: Day 1 and Day 14]

Part A: Number of Participants With AEs and SAEs [Time Frame: Day 1 up to Day 28]

Part B: Absolute Change in Height [Time Frame: From Baseline at Week 24]

Part B: Absolute Change in Body Mass Index (BMI) [Time Frame: From Baseline at Week 24]

Part B: Absolute Change in Weight [Time Frame: From Baseline at Week 24]

Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA) [Time Frame: Day 1 and Day 14]

Part B: Absolute Change in Sweat Chloride [Time Frame: From Baseline through Week 24]

Part B: Absolute Change in Sweat Chloride [Time Frame: From Baseline through Week 4]

Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA) [Time Frame: Week 16]

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

Secondary ID(s)

2017-001164-38

VX15-661-113

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02953314