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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: IVA

Study type: Interventional

Funder types: Industry

Identifiers

NCT02725567

2015-001997-16 (EudraCT Number)

VX15-770-124

Details and patient eligibility

About

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.

Enrollment: 57 patients

Sex: All

Ages: 1 to 24 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 2 patient groups

Part A: 3 to <24 months

Experimental group

Description:

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.

Treatment:

Drug: IVA

Part B + A/B:1 to < 24 months

Experimental group

Description:

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.

Treatment:

Drug: IVA