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
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
2 other identifiers
interventional
57
5 countries
23
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jun 2016
Longer than P75 for phase_3
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 14, 2016
CompletedFirst Posted
Study publicly available on registry
April 1, 2016
CompletedStudy Start
First participant enrolled
June 2, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 28, 2022
CompletedResults Posted
Study results publicly available
September 7, 2023
CompletedSeptember 7, 2023
August 1, 2023
6.1 years
March 14, 2016
June 27, 2023
August 14, 2023
Conditions
Outcome Measures
Primary Outcomes (4)
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Day 1 through Day 70
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
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)
Day 1 through Week 38
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
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 (2)
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
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
From Baseline at Week 24
Study Arms (2)
Part A: 3 to <24 months
EXPERIMENTALParticipants 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.
Part B + A/B:1 to < 24 months
EXPERIMENTALParticipants 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.
Interventions
Granules in sachet for oral administration.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Unknown Facility
Birmingham, Alabama, United States
Unknown Facility
Palo Alto, California, United States
Unknown Facility
Atlanta, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Indianapolis, Indiana, United States
Unknown Facility
Baltimore, Maryland, United States
Unknown Facility
Boston, Massachusetts, United States
Unknown Facility
Kansas City, Missouri, United States
Unknown Facility
Columbus, Ohio, United States
Unknown Facility
Philadelphia, Pennsylvania, United States
Unknown Facility
Houston, Texas, United States
Unknown Facility
Seattle, Washington, United States
Unknown Facility
Madison, Wisconsin, United States
Unknown Facility
Parkville, Victoria, Australia
Unknown Facility
South Brisbane, Australia
Unknown Facility
Westmead, Australia
Unknown Facility
Toronto, Canada
Unknown Facility
Dublin, Ireland
Unknown Facility
Edinburgh, United Kingdom
Unknown Facility
Leicester, United Kingdom
Unknown Facility
London, United Kingdom
Unknown Facility
Manchester, United Kingdom
Unknown Facility
Oxford, United Kingdom
Related Publications (2)
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.
PMID: 33023304DERIVEDRosenfeld 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.
PMID: 29886024DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 14, 2016
First Posted
April 1, 2016
Study Start
June 2, 2016
Primary Completion
June 28, 2022
Study Completion
June 28, 2022
Last Updated
September 7, 2023
Results First Posted
September 7, 2023
Record last verified: 2023-08