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 at Treatment Initiation and Have an Ivacaftor-responsive CFTR Mutation

Vertex Pharmaceuticals Incorporated0 sites35 target enrollmentMarch 7, 2016

DrugsKalydeco

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: Vertex Pharmaceuticals Incorporated
Enrollment: 35
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

March 7, 2016

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Vertex Pharmaceuticals Incorporated

Eligibility Criteria

Inclusion Criteria

•1\.Male or female with confirmed diagnosis of CF, defined as a sweat chloride value \=60 mmol/L by quantitative pilocarpine iontophoresis OR 2 CF causing mutations.
•A sweat chloride test must be performed if the sweat chloride value is not available in the subject’s medical records and the value is needed to establish eligibility. For subjects with sweat chloride values documented in their medical records and for whom it is not needed to establish eligibility, the sweat chloride test at screening is optional.
•2\.Have 1 of the following 9 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D. Subjects who have an R117H\-CFTR mutation will be eligible in regions where ivacaftor is approved for use in subjects with an R117H\-CFTR mutation. Subjects eligible for Part A/B Cohort 8 may also have other ivacaftor\-responsive mutations.
•If a genotype test has been performed previously and is documented in the subject’s medical record, the subject's eligibility must be approved by the Vertex medical monitor. If a historic genotype result is not available at screening or if the historic genotype result is not approved by the Vertex medical monitor, the subject will be tested for CFTR genotype at screening and the results must be reviewed before the first dose of ivacaftor. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility will not receive study drug.
•Subjects who have an ivacaftor\-responsive mutation on at least 1 allele will be eligible to enroll in Part A/B Cohort 8 in regions where ivacaftor is approved (consistent with the approved mutations in the region).
•oSubjects must be \=1 to \<4 months of age, \=38 weeks gestation, and weigh \=3 kg at Day 1 (treatment initiation); subjects 3 months of age must weigh \=5 kg on Day 1
•oSubjects must have a documented genotype test (performed to applicable national standards). Genotype testing is expected to be initiated prior to screening. Results of the genotype test are to be reviewed and approved by the Vertex medical monitor prior to Day 1\.
•?Subjects with the R117H genotype should have the 5T variant or a sweat chloride value \=60 mmol/L by quantitative pilocarpine iontophoresis.
•3\.Aged 0 to \<24 months at Day 1; subjects who completed Part A who are \=24 months of age on Day 1 in Part B are not eligible to enroll in Part B.
•4\.For Cohorts 7 and 8 only, gestational age \=38 weeks.

Exclusion Criteria

•1\.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.
•2\.An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
•3\.This exclusion criterion is waived for subjects enrolling in Part A/B Cohort 8\. Colonization with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening. The investigator could be guided by the following suggested criteria for a subject to be considered free of colonization:
•The subject should have had 2 respiratory tract cultures negative for these organisms within the past 12 months, with no subsequent positive cultures.
•These 2 respiratory tract cultures should have been separated by at least 3 months.
•One of these 2 respiratory tract cultures should have been obtained within the past 6 months.
•4\.Abnormal liver function at screening or any prior history of clinically relevant elevated (\>2 × upper limit of normal \[ULN]) serum aspartate transaminase (AST), serum alanine transaminase (ALT), or bilirubin (excluding newborn hyperbilirubinemia)
•5\.History of solid organ or hematological transplantation
•6\.Any clinically significant non\-CF\-related illness within 2 weeks before Day 1\. Illness is defined as an acute (serious or nonserious) condition (e.g., gastroenteritis)
•7\.Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1