A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation

August 14, 2023 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3, 2 Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation

The purpose of this study was to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in participants with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) gene mutation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

57

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • South Brisbane, Australia
      • Westmead, Australia
    • Victoria
      • Parkville, Victoria, Australia
  • Canada
      • Toronto, Canada
  • Ireland
      • Dublin, Ireland
  • United Kingdom
      • Edinburgh, United Kingdom
      • Leicester, United Kingdom
      • London, United Kingdom
      • Manchester, United Kingdom
      • Oxford, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • California
      • Palo Alto, California, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • Missouri
      • Kansas City, Missouri, United States
    • Ohio
      • Columbus, Ohio, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • Houston, Texas, United States
    • Washington
      • Seattle, Washington, United States
    • Wisconsin
      • Madison, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 2 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of CF by sweat chloride value or CF mutation criteria.
  • Have 1 of the following 10 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H (eligible in regions where ivacaftor is approved for use). Part A/B group may also have other ivacaftor-responsive mutations.
  • Hematology, serum chemistry, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator.

Exclusion Criteria:

  • 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 study drug to the participant
  • Colonization with organisms associated with a more rapid decline in pulmonary status at screening (Only for Parts A and B)
  • History of abnormal liver function or abnormal liver function at screening
  • History of solid organ or hematological transplantation
  • Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
  • Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening
  • Hemoglobin (Hgb) <9.5 g/dL at screening
  • Chronic kidney disease of Stage 3 or above
  • Presence of a non-congenital or progressive lens opacity or cataract at Screening

Other protocol defined Inclusion/Exclusion Criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: 3 to <24 months
Participants weighing 5 to less than (<) 7 kilogram (kg) received 25 milligram (mg) IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4.
Drug: IVA
Granules in sachet for oral administration.
Other Names:
  • VX-770
  • ivacaftor
Experimental: Part B + A/B:1 to < 24 months
Participants 4 to <6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to <7 kg received 25 mg IVA, 7 to <14 kg received 50 mg IVA, and those weighing 14 to <25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to <4 months weighing 3 kg to <5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
Drug: IVA
Granules in sachet for oral administration.
Other Names:
  • VX-770
  • ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time Frame: Day 1 through Day 70
Day 1 through Day 70
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time Frame: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time Frame: Day 1 through Week 38
Day 1 through Week 38
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time Frame: Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time Frame: Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
Time Frame: From Baseline at Week 24
Sweat samples were collected using an approved collection device.
From Baseline at Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 2, 2016

Primary Completion (Actual)

June 28, 2022

Study Completion (Actual)

June 28, 2022

Study Registration Dates

First Submitted

March 14, 2016

First Submitted That Met QC Criteria

March 31, 2016

First Posted (Estimated)

April 1, 2016

Study Record Updates

Last Update Posted (Actual)

September 7, 2023

Last Update Submitted That Met QC Criteria

August 14, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX15-770-124
  • 2015-001997-16 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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