Clinical trial NCT02725567: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2016-04-01
Enrollment: 57
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 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.

Primary outcomes:
measure: Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
timeFrame: Day 1 through Day 70
measure: Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
timeFrame: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
measure: Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
timeFrame: Day 1 through Week 38
measure: Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
timeFrame: 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 outcomes:
measure: Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
timeFrame: 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)
measure: Part B + A/B: Absolute Change From Baseline in Sweat Chloride
timeFrame: From Baseline at Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Palo Alto
country: United States
state: California
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Kansas City
country: United States
state: Missouri
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Parkville
country: Australia
state: Victoria
city: South Brisbane
country: Australia
city: Westmead
country: Australia
city: Toronto
country: Canada
city: Dublin
country: Ireland
city: Edinburgh
country: United Kingdom
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
References:
citation: 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.
citation: 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.