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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03691779
Other study ID # VX18-445-106
Secondary ID 2018-001695-38
Status Completed
Phase Phase 3
First received
Last updated
Start date October 2, 2018
Est. completion date August 7, 2020

Study information

Verified date August 2021
Source Vertex Pharmaceuticals Incorporated
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 71
Est. completion date August 7, 2020
Est. primary completion date August 7, 2020
Accepts healthy volunteers No
Gender All
Age group 6 Years to 11 Years
Eligibility Key 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. Key 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
ELX/TEZ/IVA
Fixed-dose combination tablet orally once daily in the morning.
IVA
IVA tablet orally once daily in the evening.

Locations

Country Name City State
Australia Queensland Children's Hospital South Brisbane
Australia The Children's Hospital at Westmead Westmead
Canada The Hospital for Sick Children Toronto
Canada British Columbia's Children's Hospital Vancouver
Ireland Children's Health Ireland at Crumlin Dublin
Ireland Children's Health Ireland at Temple Street Dublin
United Kingdom Birmingham Children's Hospital Birmingham
United Kingdom Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital London
United States Children's Hospital Colorado Aurora Colorado
United States Boston Children's Hospital Boston Massachusetts
United States Clinical Research of Charlotte Charlotte North Carolina
United States Ann & Robert Lurie Children's Hospital of Chicago Chicago Illinois
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 Texas Children's Hospital Houston Texas
United States The Children's Mercy Hospital Kansas City Missouri
United States Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota Minneapolis Minnesota
United States Northwell Health- Long Island Jewish Medical Center New Hyde Park New York
United States Children's Hospital of Orange County Orange California
United States Oregon Health & Science University Portland Oregon
United States Seattle Children's Hospital Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA Part A: Day 15
Primary Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA Part A: Day 15
Primary 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
Primary 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 Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) Part A: Day 15
Secondary Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) Part A: Day 15
Secondary Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ) Part A: Day 15
Secondary Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA) 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: Day 15
Secondary 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)
Secondary Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B: From Baseline Through Week 24
Secondary Part B: Absolute Change in Sweat Chloride (SwCl) Sweat samples were collected using an approved collection device. Part B: From Baseline Through Week 24
Secondary Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score 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: From Baseline Through Week 24
Secondary Part B: Absolute Change in Body Mass Index (BMI) BMI was defined as weight in kg divided by squared height in meters (m^2). Part B: From Baseline at Week 24
Secondary Part B: Absolute Change in BMI For-Age Z-Score 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: From Baseline at Week 24
Secondary Part B: Absolute Change in Weight Part B: From Baseline at Week 24
Secondary Part B: Absolute Change in Weight-for-age Z-Score 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: From Baseline at Week 24
Secondary Part B: Absolute Change in Height Part B: From Baseline at Week 24
Secondary Part B: Absolute Change in Height-for-Age Z-Score 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: From Baseline at Week 24
Secondary Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale 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: At Week 24
Secondary Part B: Number of Pulmonary Exacerbations Events 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: From Baseline Through Week 24
Secondary Part B: Number of CF Related Hospitalizations The total number of CF related hospitalization events across all participants were reported. Part B: From Baseline Through Week 24
Secondary 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
Secondary Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5) 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. Part B: From Baseline Through Week 24
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