Clinical trial NCT03691779: Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2018-10-02
Enrollment: 71
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA
timeFrame: Part A: Day 15
measure: Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA
timeFrame: Part A: Day 15
measure: Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA
timeFrame: Part A: Day 15
measure: Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)
Secondary outcomes:
measure: Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
timeFrame: Part A: Day 15
measure: Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)
timeFrame: Part A: Day 15
measure: Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)
timeFrame: Part A: Day 15
measure: Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)
timeFrame: Part A: Day 15
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs
timeFrame: Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)
measure: Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: Part B: From Baseline Through Week 24
measure: Part B: Absolute Change in Sweat Chloride (SwCl)
timeFrame: Part B: From Baseline Through Week 24
measure: Part B: Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
timeFrame: Part B: From Baseline Through Week 24
measure: Part B: Absolute Change in Body Mass Index (BMI)
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Absolute Change in BMI For-Age Z-Score
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Absolute Change in Weight
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Absolute Change in Weight-for-age Z-Score
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Absolute Change in Height
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Absolute Change in Height-for-Age Z-Score
timeFrame: Part B: From Baseline at Week 24
measure: Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale
timeFrame: Part B: At Week 24
measure: Part B: Number of Pulmonary Exacerbations Events
timeFrame: Part B: From Baseline Through Week 24
measure: Part B: Number of CF Related Hospitalizations
timeFrame: Part B: From Baseline Through Week 24
measure: Part B: Ctrough of ELX, ELX Metabolite (M23-ELX), TEZ, TEZ Metabolite (M1-TEZ), IVA and IVA Metabolite (M1-IVA)
timeFrame: Part B: At Week 4
measure: Part B: Absolute Change in Lung Clearance Index 2.5 (LCI2.5)
timeFrame: Part B: From Baseline Through Week 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
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: New Hyde Park
country: United States
facility: Northwell Health- Long Island Jewish Medical Center
state: New York
city: Charlotte
country: United States
facility: Clinical Research of Charlotte
state: North Carolina
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: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: Vancouver
country: Canada
facility: British Columbia's Children's Hospital
city: Dublin
country: Ireland
facility: Children's Health Ireland at Crumlin
city: Dublin
country: Ireland
facility: Children's Health Ireland at Temple Street
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
Study officials:
References:
citation: Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA. A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2021 Jun 15;203(12):1522-1532. doi: 10.1164/rccm.202102-0509OC.
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.