A Study to Evaluate Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Aged 3 Through 5 Years Who Have a Specified CFTR Gating Mutation

NCT02742519 | Terminated Phase 3 Results DMC

• 2 other identifiers: VX15-770-1232015-001267-39
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 6

Brief Summary

To evaluate the efficacy of ivacaftor treatment, as measured by lung clearance index (LCI), in subjects with cystic fibrosis (CF) who have a specified CF transmembrane conductance regulator (CFTR) gating mutation

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Lung Clearance Index (LCI2.5) Through 8 Weeks of Treatment (Average of Week 4 and Week 8 LCI2.5)

  LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

  Baseline Through Week 8 for each treatment period, Up to 24 Weeks

Secondary Outcomes (5)

• Absolute Change From Baseline in Immunoreactive Trypsinogen Levels at Week 8

  Baseline and Week 8 of each treatment period, Up to 24 Weeks

• Absolute Change From Baseline in Fecal Elastase-1 Levels at Week 8

  Baseline and Week 8 of each treatment period, Up to 24 Weeks

• Absolute Change From Baseline in Weight at Week 8

  Baseline and Week 8 of each treatment period, Up to 24 Weeks

• Absolute Change From Baseline in Body Mass Index (BMI) at Week 8

  Baseline and Week 8 of each treatment period, Up to 24 Weeks

• Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to Month 15

Study Arms (3)

Part 1-Sequence 1

EXPERIMENTAL

ivacaftor in Treatment Period 1 →washout→placebo in Treatment Period 2

Drug: ivacaftor; Drug: Placebo

Part 1 - Sequence 2

EXPERIMENTAL

placebo in Treatment Period 1→washout→ivacaftor in Treatment Period 2

Drug: ivacaftor; Drug: Placebo

Part 2: ivacaftor

EXPERIMENTAL

open label period

Drug: ivacaftor

Interventions

ivacaftor DRUG

Also known as: VX-770

Part 1 - Sequence 2; Part 1-Sequence 1; Part 2: ivacaftor

Placebo DRUG

Part 1 - Sequence 2; Part 1-Sequence 1

Eligibility Criteria

• Age: 3 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 1 of the following CFTR gating mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D.
• Hematology, serum chemistry, and coagulation at Screening with no clinically significant abnormalities or concomitant diagnosis that would interfere with the LCI and CT scan study assessments, as judged by the investigator.

You may not qualify if:

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
• Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (in the opinion of the investigator)
• Abnormal liver function, at Screening, defined as ≥3 × upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), and total bilirubin
• History of solid organ or hematological transplantation
• Any clinically significant "non-CF-related" illness within 2 weeks before Day 1
• 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 (whichever is longer or as determined by the local requirements) before Screening

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (6)

Unknown Facility

Parkville, Victoria, Australia

Location

Unknown Facility

South Brisbane, Australia

Location

Unknown Facility

Subiaco, Australia

Location

Unknown Facility

Westmead, Australia

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

London, United Kingdom

Location

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

Limitations and Caveats

Vertex terminated the study early because of enrollment futility.

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2016
• First Posted: April 19, 2016
• Study Start: May 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: November 19, 2018
• Results First Posted: November 19, 2018

Record last verified: 2018-10

Locations

AU (4); GB (1); CA (1)