A Study Evaluating Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis and F/MF Genotypes

A Phase 3b, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects 6 Through 11 Years of Age Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

This study will evaluate the efficacy and safety of elexacaftor (ELX) / tezacaftor (TEZ) / ivacaftor (IVA) triple combination (TC) in subjects 6 through 11 years of age with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function (MF) mutation (F/MF genotypes).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Other: Placebo (matched to ELX/TEZ/IVA); Other: Placebo (matched to IVA); Drug: ELX/TEZ/IVA; Drug: IVA

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia
    • Telethon Kids Institute
  • South Brisbane, Australia
    • Queensland CHILDREN'S HOSPITAL
  • Westmead, Australia
    • The Children's Hospital at Westmead
• Canada
  • Montréal, Canada
    • McGill University Health Centre, Glen Site, Montreal Children's Hospital
  • Toronto, Canada
    • The Hospital for Sick Children
  • Vancouver, Canada
    • British Columbia Children's Hospital
• Denmark
  • Copenhagen, Denmark
    • Juliane Marie Center, Rigshospitalet
• France
  • Bordeaux cedex, France
    • Groupe Hospitaler Pellegrin, CHU De Bordeaux
  • Bron Cedex, France
    • CHU Lyon - Hopital Femme Mere-Enfant
  • Paris, France
    • Hôpital Robert Debré
  • Paris Cedex 15, France
    • Hopital Necker, Enfants Malades
  • Roscoff cedex, France
    • Centre de Perharidy
• Germany
  • Berlin, Germany
    • Charite Paediatric Pulmonology Department
  • Essen, Germany
    • Universitatsklinikum Essen
  • Frankfurt, Germany
    • Johann Wolfgang Goethe University
  • Gießen, Germany
    • Justus-Liebig-Universität Gießen Zentrum für Kinderheilkunde und Jugendmedizin
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitaetsklinikum Heidelberg, Zenter fuer Kinder-und Jugendmedizin
  • Koeln, Germany
    • Universitaetsklinkum Koeln, CF-Studienzentrum
• Israel
  • Jerusalem, Israel
    • Hadassah University Hospital Mount Scopus
  • Petah Tikva, Israel
    • Schneider Children's Medical Center
• Netherlands
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen
  • Rotterdam, Netherlands
    • Erasmus Medical Center / Sophia Children's Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall D Hebron
  • Murcia, Spain
    • Hospital Virgen de la Arrixaca
• Switzerland
  • Bern, Switzerland
    • Inselspital - Universitaetsspital Bern
  • Zurich, Switzerland
    • Kinderspital Zuerich
• United Kingdom
  • Bristol, United Kingdom
    • University Hospitals Bristol and Weston NHS Foundation Trust, Bristol Royal Hospital
  • Cardiff, United Kingdom
    • Children's Hospital of Wales
  • Edinburgh, United Kingdom
    • Royal Hospital for Sick Children
  • Liverpool, United Kingdom
    • Alder Hey Children's NHS Foundation Trust
  • London, United Kingdom
    • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
  • London, United Kingdom
    • Great Ormond Street Hospital for Sick Children
  • Southampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Heterozygous for the F508del mutation (F/MF)
• Forced expiratory volume in 1 second (FEV1) value greater than equal to(≥) 70%

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks.	Other: Placebo (matched to ELX/TEZ/IVA); Placebo matched to ELX/TEZ/IVA for oral administration once daily (qd) in the morning.; Other: Placebo (matched to IVA); Placebo matched to IVA for oral administration qd in the evening.
Experimental: ELX/TEZ/IVA; Participants weighing less than (<) 30 kilograms (kg) at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and participants weighing greater than equals to (>=) 30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.	Drug: ELX/TEZ/IVA; Fixed-dose combination tablet for oral administration qd in the morning.; Other Names: VX-445/VX-661/VX-770; elexacaftor/tezacaftor/ivacaftor; Drug: IVA; Tablet for oral administration qd in the evening.; Other Names: VX-770; ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Lung Clearance Index 2.5 (LCI2.5)	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.	From Baseline Through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Sweat Chloride (SwCl)	Sweat samples were collected using an approved collection device.	From Baseline Through Week 24
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 28

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2020
• Primary Completion (Actual): May 17, 2021
• Study Completion (Actual): May 17, 2021

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor; Elexacaftor
• Other Study ID Numbers: VX19-445-116; 2019-003554-86 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes