Clinical trial NCT05422222: Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2022-06-16
Enrollment: 210
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene

Key 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.

Primary outcomes:
measure: Part A: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites
timeFrame: From Day 1 up to Day 22
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to Day 50
measure: Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to Week 28
Secondary outcomes:
measure: Part B: Absolute Change in Sweat Chloride (SwCl)
timeFrame: From Baseline Through Week 24
measure: Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites
timeFrame: From Day 1 up to Week 16
measure: Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale
timeFrame: At Day 1 and Week 24
measure: Part B: Absolute Change in Percent Predicted Forced Expiratory Volume (ppFEV1)
timeFrame: From Baseline Through Week 24
measure: Part B: Number of Pulmonary Exacerbation (PEx)
timeFrame: From Baseline Through Week 24
measure: Part B: Number of CF-Related Hospitalizations
timeFrame: From Baseline Through Week 24
measure: Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score
timeFrame: From Baseline Through Week 24
measure: Part B: Absolute Change in Body Mass Index (BMI)
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in BMI-for-age Z-score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Weight
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Weight-for-age Z-score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Weight-for-length
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Weight-for-length Z-score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Height
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Height-for-age Z-score
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Length
timeFrame: From Baseline at Week 24
measure: Part B: Absolute Change in Length-for-age Z-score
timeFrame: From Baseline at Week 24
measure: Part B: Proportion of Participants With SwCl <60 millimole per liter (mmol/L)
timeFrame: From Baseline Through Week 24
measure: Part B: Proportion of Participants With SwCl <30 mmol/L
timeFrame: From Baseline Through Week 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University Clinical and Translational Research Unit
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: The Emory Clinic / Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine / St. Louis Children's Hospital
state: Missouri
city: Lake Success
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital - Wallace Tower
state: Texas
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Madison
country: United States
facility: American Family Childrens Hospital
state: Wisconsin
city: Nedlands
country: Australia
facility: The Kids Research Institute Australia
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
city: Parkville
country: Australia
facility: The Royal Children's Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
city: Bron Cedex
country: France
facility: CHU Lyon - Hopital Femme Mere-Enfant
city: Paris Cedex 15
country: France
facility: Hopital Necker, Enfants Malades
city: Berlin
country: Germany
facility: Charité Universitätsmedizin BerlinX
city: Essen
country: Germany
facility: Kinderklinik III, Abt. fur Pneumologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center / Sophia Children's Hospital
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Bern
country: Switzerland
facility: Inselspital - Universitaetsspital Bern
city: Zurich
country: Switzerland
facility: Kinderspital Zurich
city: Cardiff
country: United Kingdom
facility: Children and Young Adults Research Unit
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
References: