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Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years

Phase 3
Completed
Conditions
Cystic Fibrosis
Interventions
Registration Number
NCT04537793
Lead Sponsor
Vertex Pharmaceuticals Incorporated
Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
83
Inclusion Criteria
  • Homozygous for the F508del mutation or heterozygous for F508del and a minimal function (MF) mutation (F/F or F/MF genotypes)

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

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A: ELX/TEZ/IVAIVAParticipants weighing greater than or equal to (\>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days.
Part B: ELX/TEZ/IVAIVAParticipants weighing (\>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (\>=)10 kg to less than (\<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks.
Part A: ELX/TEZ/IVAELX/TEZ/IVAParticipants weighing greater than or equal to (\>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days.
Part B: ELX/TEZ/IVAELX/TEZ/IVAParticipants weighing (\>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (\>=)10 kg to less than (\<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant MetabolitesFrom Day 1 through Day 15
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)From Day 1 up to Day 43
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)From Day 1 up to Week 28
Secondary Outcome Measures
NameTimeMethod
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant MetabolitesFrom Day 1 through Week 16
Part B: Absolute Change in Sweat Chloride (SwCl)From Baseline through Week 24

Sweat samples were collected using an approved collection device.

Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5)From Baseline through Week 24

The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.

Trial Locations

Locations (22)

UPMC Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

Banner University of Arizona Medical Center

🇺🇸

Tucson, Arizona, United States

Stanford University

🇺🇸

Palo Alto, California, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Children's Hospital of Colorado

🇺🇸

Aurora, Colorado, United States

Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Riley Hospital for Children at Indiana University Health

🇺🇸

Indianapolis, Indiana, United States

The Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

British Columbia Children's Hospital

🇨🇦

Vancouver, Canada

The Royal Children's Hospital

🇦🇺

Parkville, VIC, Australia

Queensland Children's Hospital

🇦🇺

South Brisbane, Australia

NC TraCS Institute - CTRC University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie

🇩🇪

Essen, Germany

Charite Paediatric Pulmonology Department

🇩🇪

Berlin, Germany

Alder Hey Children's NHS Foundation Trust

🇬🇧

Liverpool, United Kingdom

Washington University School of Medicine / St. Louis Children's Hospital

🇺🇸

Saint Louis, Missouri, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

The Hospital for Sick Children

🇨🇦

Toronto, Canada

Telethon Kids Institute

🇦🇺

Nedlands, Australia

Royal Brompton Hospital

🇬🇧

London, United Kingdom

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