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

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ClinicalTrials.gov Identifier: NCT02725567

Recruitment Status : Recruiting

First Posted : April 1, 2016

Last Update Posted : December 22, 2020

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Sponsor:

Information provided by (Responsible Party):

Vertex Pharmaceuticals Incorporated

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in subjects 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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: ivacaftor	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	March 2016
Estimated Primary Completion Date :	July 2022
Estimated Study Completion Date :	July 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Ivacaftor

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A Group 1: Participants 12 to < 24 months Group 2: Participants 6 to < 12 months (enrollment begins after an assessment of data from Group 1) Group 3: Participants 3 to < 6 months (enrollment begins after an assessment of data from Group 2)	Drug: ivacaftor Other Name: Kalydeco
Experimental: Part B Group 5: Participants 12 to < 24 months (enrollment begins after an assessment of data from Part A, Group 1) Group 6: Participants 6 to < 12 months (enrollment begins after an assessment of data from Part A, Group 2) Group 7: Participants 4 to < 6 months (enrollment begins after an assessment of data from Part A, Group 3)	Drug: ivacaftor Other Name: Kalydeco
Experimental: Part A/B - Group 8: Participants 1 to < 4 months of age	Drug: ivacaftor Other Name: Kalydeco

Outcome Measures

Primary Outcome Measures :

Part A: Safety, as determined by number of subjects with adverse events (AEs), clinically relevant abnormal laboratory values (serum chemistry and hematology), standard 12 lead electrocardiograms (ECGs), vital signs, and ophthalmologic examinations [ Time Frame: Day 1 up to Day 70 ]
Part B: Safety, as determined by number of subjects with adverse events (AEs), clinically relevant abnormal laboratory values (serum chemistry and hematology), standard 12 lead electrocardiograms (ECGs), vital signs, and ophthalmologic examinations [ Time Frame: Day 1 up to Week 24 ]
Part A: Peak concentrations (C3-6h) of ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: after 4 days of ivacaftor treatment ]
Part A: Trough concentrations (Ctrough) of ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: after 4 days of ivacaftor treatment ]
Part A/B: Safety, as determined by number of subjects with adverse events (AEs), clinically relevant abnormal laboratory values (serum chemistry and hematology), standard 12 lead electrocardiograms (ECGs), vital signs, and ophthalmologic examinations [ Time Frame: Day 1 up to Week 24 ]
Part A/B: Trough concentrations (Ctrough) of ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: after 4 days of ivacaftor treatment ]

Secondary Outcome Measures :

Part B: Peak concentrations (C3-6h) of ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: through Week 24 ]
Part B: Trough concentrations (Ctrough) of ivacaftor, M1 ivacaftor, and M6 ivacaftor [ Time Frame: through Week 24 ]
Part B: Absolute change from baseline in sweat chloride using quantitative pilocarpine iontophoresis [ Time Frame: up to Week 24 ]
Part A/B: Absolute change from baseline in sweat chloride using quantitative pilocarpine iontophoresis [ Time Frame: up to Week 24 ]

Eligibility Criteria

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Ages Eligible for Study:	up to 24 Months (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 subject
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02725567

Contacts

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Contact: Medical Information	617-341-6777	medicalinfo@vrtx.com

Locations

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

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Davies JC, Wainwright CE, Sawicki GS, Higgins MN, Campbell D, Harris C, Panorchan P, Haseltine E, Tian S, Rosenfeld M. Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial. Am J Respir Crit Care Med. 2021 Mar 1;203(5):585-593. doi: 10.1164/rccm.202008-3177OC.

Rosenfeld M, Wainwright CE, Higgins M, Wang LT, McKee C, Campbell D, Tian S, Schneider J, Cunningham S, Davies JC; ARRIVAL study group. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir Med. 2018 Jul;6(7):545-553. doi: 10.1016/S2213-2600(18)30202-9. Epub 2018 Jun 7. Erratum in: Lancet Respir Med. 2018 Jul;6(7):e35. Lancet Respir Med. 2019 Apr;7(4):e15.

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Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT02725567
Other Study ID Numbers:	VX15-770-124 2015-001997-16 ( EudraCT Number )
First Posted:	April 1, 2016 Key Record Dates
Last Update Posted:	December 22, 2020
Last Verified:	December 2020

Additional relevant MeSH terms:

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Cystic Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases	Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action

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