A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age
Overview
- Phase
- Phase 3
- Intervention
- ELX/TEZ/IVA
- Conditions
- Cystic Fibrosis
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 71
- Locations
- 21
- Primary Endpoint
- Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
- •Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height.
Exclusion Criteria
- •Clinically significant cirrhosis with or without portal hypertension
- •Lung infection with organisms associated with a more rapid decline in pulmonary status.
- •Solid organ or hematological transplantation.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Part A: ELX/TEZ/IVA
Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.
Intervention: ELX/TEZ/IVA
Part A: ELX/TEZ/IVA
Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.
Intervention: IVA
Part B: ELX/TEZ/IVA
Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Intervention: ELX/TEZ/IVA
Part B: ELX/TEZ/IVA
Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.
Intervention: IVA
Outcomes
Primary Outcomes
Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
Time Frame: Part A: Day 15
Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA
Time Frame: Part A: Day 15
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA
Time Frame: Part A: Day 15
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
Secondary Outcomes
- Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)(Part A: Day 15)
- Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs(Part A: Day 1 Through Safety Follow-up Visit (up to Day 43))
- Part B: Absolute Change in Sweat Chloride (SwCl)(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in Body Mass Index (BMI)(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Weight-for-age Z-Score(Part B: From Baseline at Week 24)
- Part B: Number of CF Related Hospitalizations(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(Part B: From Baseline Through Week 24)
- Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)(Part A: Day 15)
- Part B: Number of Pulmonary Exacerbations Events(Part B: From Baseline Through Week 24)
- Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)(Part B: At Week 4)
- Part B: Absolute Change in Weight(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Height(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score(Part B: From Baseline Through Week 24)
- Part B: Absolute Change in BMI For-Age Z-Score(Part B: From Baseline at Week 24)
- Part B: Absolute Change in Height-for-Age Z-Score(Part B: From Baseline at Week 24)
- Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale(Part B: At Week 24)
- Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)(Part B: From Baseline Through Week 24)