A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-121/Tezacaftor/Deutivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 1 Through 11 Years of Age
Overview
- Phase
- Phase 3
- Intervention
- VX-121/TEZ/D-IVA
- Conditions
- Cystic Fibrosis
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 210
- Locations
- 38
- Primary Endpoint
- Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants with at least 1 triple combination responsive (TCR) mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene
Exclusion Criteria
- •History of solid organ, hematological transplantation, or cancer
- •Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
- •Lung infection with organisms associated with a more rapid decline in pulmonary status
- •Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Part A: VX-121/TEZ/D-IVA
Participants will receive VX-121/TEZ/D-IVA in the morning.
Intervention: VX-121/TEZ/D-IVA
Part B: VX-121/TEZ/D-IVA
Participants will receive VX-121/TEZ/D-IVA in the morning with the dose(s) to be based on the outcome of Part A.
Intervention: VX-121/TEZ/D-IVA
Outcomes
Primary Outcomes
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From Day 1 up to Day 50
Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From Day 1 up to Week 28
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites
Time Frame: From Day 1 up to Day 22
Secondary Outcomes
- Part B: Absolute Change in Body Mass Index (BMI)(From Baseline at Week 24)
- Part B: Absolute Change in BMI-for-age Z-score(From Baseline at Week 24)
- Part B: Absolute Change in Weight-for-age Z-score(From Baseline at Week 24)
- Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites(From Day 1 up to Week 16)
- Part B: Absolute Change in Percent Predicted Forced Expiratory Volume (ppFEV1)(From Baseline Through Week 24)
- Part B: Proportion of Participants With SwCl <30 mmol/L(From Baseline Through Week 24)
- Part B: Number of CF-Related Hospitalizations(From Baseline Through Week 24)
- Part B: Absolute Change in Weight(From Baseline at Week 24)
- Part B: Absolute Change in Weight-for-length(From Baseline at Week 24)
- Part B: Absolute Change in Height(From Baseline at Week 24)
- Part B: Absolute Change in Height-for-age Z-score(From Baseline at Week 24)
- Part B: Absolute Change in Sweat Chloride (SwCl)(From Baseline Through Week 24)
- Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale(At Day 1 and Week 24)
- Part B: Number of Pulmonary Exacerbation (PEx)(From Baseline Through Week 24)
- Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score(From Baseline Through Week 24)
- Part B: Absolute Change in Length(From Baseline at Week 24)
- Part B: Absolute Change in Length-for-age Z-score(From Baseline at Week 24)
- Part B: Absolute Change in Weight-for-length Z-score(From Baseline at Week 24)
- Part B: Proportion of Participants With SwCl <60 millimole per liter (mmol/L)(From Baseline Through Week 24)