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

• ClinicalTrials.gov Identifier: NCT02725567
• Recruitment Status: Completed
• First Posted: April 1, 2016
• Results First Posted: September 7, 2023
• Last Update Posted: September 7, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: March 14, 2016
• First Posted Date: April 1, 2016
• Results First Submitted Date: June 27, 2023
• Results First Posted Date: September 7, 2023
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: June 2, 2016
• Actual Primary Completion Date: June 28, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 14, 2023)

• Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) [ Time Frame: Day 1 through Day 70 ]
• Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) [ Time Frame: 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) [ Time Frame: Day 1 through Week 38 ]
• Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) [ Time Frame: 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) ]

Original Primary Outcome Measures (submitted: March 31, 2016)

• 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 ]

Current Secondary Outcome Measures (submitted: August 14, 2023)

• Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA) [ Time Frame: 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 [ Time Frame: From Baseline at Week 24 ]
  Sweat samples were collected using an approved collection device.

Original Secondary Outcome Measures (submitted: March 31, 2016)

• 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: through Week 24 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

Drug: IVA

Granules in sachet for oral administration.

Other Names:

• VX-770
• ivacaftor

Study Arms

• Experimental: Part A: 3 to <24 months
  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.
  Intervention: Drug: IVA
• Experimental: Part B + A/B:1 to < 24 months
  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.
  Intervention: Drug: IVA

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 14, 2023): 57
• Original Estimated Enrollment (submitted: March 31, 2016): 30
• Actual Study Completion Date: June 28, 2022
• Actual Primary Completion Date: June 28, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month to 24 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Ireland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02725567
• Other Study ID Numbers: VX15-770-124; 2015-001997-16 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vertex Pharmaceuticals Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Vertex Pharmaceuticals Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vertex Pharmaceuticals Incorporated
• Verification Date: August 2023