Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age
- Registration Number
- NCT03691779
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 71
- 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.
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B: ELX/TEZ/IVA 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. Part B: ELX/TEZ/IVA 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. Part A: ELX/TEZ/IVA 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. Part A: ELX/TEZ/IVA 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.
- Primary Outcome Measures
Name Time Method Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA 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 Part A: Day 15 Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA 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) Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
- Secondary Outcome Measures
Name Time Method 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 The AUC data was analyzed for up to 6 hours for IVA metabolite (M1-IVA). Therefore, AUC0-6h is reported for M1-IVA metabolite.
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 Sweat samples were collected using an approved collection device.
Part B: Absolute Change in Body Mass Index (BMI) Part B: From Baseline at Week 24 BMI was defined as weight in kg divided by squared height in meters (m\^2).
Part B: Absolute Change in Weight-for-age Z-Score Part B: From Baseline at Week 24 The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Part B: Number of CF Related Hospitalizations Part B: From Baseline Through Week 24 The total number of CF related hospitalization events across all participants were reported.
Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Part B: From Baseline Through Week 24 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
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 Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. The total number of pulmonary exacerbations events across all participants were reported.
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 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.
Part B: Absolute Change in BMI For-Age Z-Score Part B: From Baseline at Week 24 BMI was defined as weight in kg divided by squared height in meters (m\^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Part B: Absolute Change in Height-for-Age Z-Score Part B: From Baseline at Week 24 The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale Part B: At Week 24 The study drug acceptability (participant reaction) was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). Number of participants with the indicated categorical response in the drug acceptability assessment were reported.
Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Part B: From Baseline Through Week 24 LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Trial Locations
- Locations (21)
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Ann & Robert Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Northwell Health- Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Clinical Research of Charlotte
🇺🇸Charlotte, North Carolina, United States
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Scroll for more (11 remaining)Children's Hospital of Orange County🇺🇸Orange, California, United States