A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Participants With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

A Phase 3, 2-Arm, Open-label Study to Evaluate the Safety and Pharmacodynamics of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in participants with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IVA

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia
    • Queensland Children's Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children
• Germany
  • Heidelberg, Germany
    • Universitaetsklinikum Heidelberg, Zenter fuer Kinder-und Jugendmedizin
• Ireland
  • Dublin, Ireland
    • Children's Health Ireland at Crumlin
  • Dublin, Ireland
    • Children's University Hospital Temple Street
  • Limerick, Ireland
    • University Hospital Limerick
• United Kingdom
  • Edinburgh, United Kingdom
    • Paediatric Clinical Research Facility
  • Liverpool, United Kingdom
    • Alder Hey Children's Alder Hey Children's NHS Foundation Trust
  • London, United Kingdom
    • Great Ormond Street Hospital for Sick Children
  • London, United Kingdom
    • Royal Brompton & Harefield NHS Founcation Trust, Royal BromptonHospital
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Trust, John Radcliffe Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Palo Alto, California, United States, 94034
      • Stanford University
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Center for Advanced Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Childrens's Hospitals and Clinics of Minnnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Hospital
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Ivacaftor Arm: Participants From Study 124 (NCT02725567 ) Part B:

• Participants transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF).

Ivacaftor Arm: Participants Not From Study 124 Part B:

• Confirmed diagnosis of CF, or 2 CF-causing mutations.
• An ivacaftor- responsive CFTR mutation on at least 1 allele. Participants will be eligible in countries/regions where ivacaftor is approved for use in participants 2 years of age and older.
• As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF.

Observational Arm:

• Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126.

Exclusion Criteria:

Ivacaftor Arm: Participants From Study 124 Part B:

• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant.
• Participants receiving commercially available ivacaftor treatment

Ivacaftor Arm: Participants Not From Study 124 Part B:

• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant
• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1
• Abnormal liver function at screening
• Hemoglobin <9.5 g/dL at screening
• History of solid organ or hematological transplantation
• Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1

Observational Arm:

• Receiving ivacaftor treatment

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational Arm
Experimental: Ivacaftor Arm; Participants less than (<) 24 months of age and weighing 5 to less than (<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to <14 kg received 50 mg IVA q12h, and those weighing 14 to <25 kg received 75 mg IVA q12h. Participants more than or equal (>=) 24 months of age and weighing <14 kg received 50 mg IVA q12h, and those weighing more than or equal to (>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and pharmacokinetic (PK) data from parent study, age and weight.	Drug: IVA; Granules for oral administration.; Other Names: VX-770; ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	Day 1 up to Week 120

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Sweat Chloride	Sweat samples were collected using an approved collection device.	From Baseline at Week 96

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: September 6, 2017
• First Submitted That Met QC Criteria: September 6, 2017
• First Posted (Actual): September 8, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX15-770-126; 2017-001379-21 (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