Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Cystic Fibrosis Clinical Trial

Official title:

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

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
• 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
• 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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

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