Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation

NCT01705145 | Completed Phase 3 Results DMC

• 2 other identifiers: VX11-770-108KIWI
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 20

Brief Summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele. Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

  AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.

  Part A: Up to 93 Days

• Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

  AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.

  Part B: Up to 28 Weeks

• Part A: Plasma Concentration of Ivacaftor and Its Metabolites

  Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.

  Part A: up to 24 hours post-dose on Day 4

Secondary Outcomes (5)

• Part B: Plasma Concentration of Ivacaftor and Its Metabolites

  Part B: up to 24 hours post-dose on Day 168

• Part B: Absolute Change From Baseline in Sweat Chloride at Week 24

  Part B: Baseline, Week 24

• Part B: Absolute Change From Baseline in Weight at Week 24

  Part B: Baseline, Week 24

• Part B: Absolute Change From Baseline in Stature at Week 24

  Part B: Baseline, Week 24

• Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24

  Baseline, Week 24

Study Arms (1)

Ivacaftor

EXPERIMENTAL

Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than \[\<\] 14 kilograms \[kg\]) or 75 mg (for participants weighing greater than or equal to \[\>=\] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing \<14 kg) or 75 mg (for participants weighing \>=14 kg) q12h for 24 weeks during Part B of the study.

Drug: Ivacaftor

Interventions

Ivacaftor DRUG

Also known as: Kalydeco, VX-770

Ivacaftor

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female with confirmed diagnosis of CF
• Must have a CFTR gating mutation in at least 1 allele
• Aged 2 through 5 years at screening and Day 1
• Weight \>= 8 kg at screening and Day 1
• Hematology, serum chemistry, coagulation, 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
• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (20)

Unknown Facility

Birmingham, Alabama, United States

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Aurora, Colorado, United States

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Atlanta, Georgia, United States

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Indianapolis, Indiana, United States

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Lexington, Kentucky, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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Omaha, Nebraska, United States

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Pittsburgh, Pennsylvania, United States

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Salt Lake City, Utah, United States

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Charlottesville, Virginia, United States

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Richmond, Virginia, United States

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Seattle, Washington, United States

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Vancouver, Canada

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Edinburgh, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

Location

Related Publications (1)

• Davies JC, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Robertson S, Green Y, Cooke J, Rosenfeld M; KIWI Study Group. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016 Feb;4(2):107-15. doi: 10.1016/S2213-2600(15)00545-7. Epub 2016 Jan 21.

  PMID: 26803277 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Study Officials

• Margaret Rosenfeld, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

• Jane Davies, MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: October 12, 2012
• Study Start: January 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 5, 2016
• Results First Posted: April 24, 2015

Record last verified: 2016-03

Locations

CA (1); US (16); GB (3)