A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor

NCT02412111 | Completed Phase 3 Results DMC

• 1 other identifier: VX14-661-109
• Study Type: interventional
• Target: 156
• Locations: 9 countries
• Sites: 63

Brief Summary

This is a Phase 3, randomized, double-blind, ivacaftor-controlled, parallel-group, multicenter study of tezacaftor in combination with ivacaftor in subjects aged 12 years and older with CF who are heterozygous for the F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  Baseline, Through Week 8

Secondary Outcomes (5)

• Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8

  Baseline, Through Week 8

• Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8

  Baseline, Through Week 8

• Absolute Change From Baseline in Sweat Chloride Through Week 8

  Baseline, Through Week 8

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to Week 16

• Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)

  Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator period

Study Arms (3)

Ivacaftor (Run-in Period)

EXPERIMENTAL

Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.

Drug: Ivacaftor

VX-661 + Ivacaftor (Active comparator period)

EXPERIMENTAL

VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.

Drug: Ivacaftor; Drug: Tezacaftor/Ivacaftor

Ivacaftor monotherapy (Active comparator period)

ACTIVE COMPARATOR

Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.

Drug: Ivacaftor

Interventions

Ivacaftor DRUG

Also known as: VX-770

Ivacaftor (Run-in Period); Ivacaftor monotherapy (Active comparator period); VX-661 + Ivacaftor (Active comparator period)

Tezacaftor/Ivacaftor DRUG

Also known as: VX-661/VX-770

VX-661 + Ivacaftor (Active comparator period)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Heterozygous for F508del-CFTR mutation and a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height during screening
• Stable CF disease as judged by the investigator.

You may not qualify if:

• History of any comorbidity 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 subject.
• Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Week -4 Visits).
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (68)

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Birmingham, Alabama, United States

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Oakland, California, United States

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San Diego, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Augusta, 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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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Lebanon, New Hampshire, United States

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Manchester, New Hampshire, United States

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Morristown, New Jersey, United States

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New Brunswick, New Jersey, United States

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Albany, New York, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Morgantown, West Virginia, United States

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Chermside, Australia

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Clayton, Australia

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Melbourne, Australia

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South Brisbane, Australia

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Westmead, Australia

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Innsbruck, Austria

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Brussels, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Calgary, Canada

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Toronto, Canada

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Vancouver, Canada

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Paris, France

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Dresden, Germany

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Erlangen, Germany

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Essen, Germany

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Frankfurt, Germany

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Giessen, Germany

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Heidelberg, Germany

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Jena, Germany

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München, Germany

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Cork, Ireland

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Dublin, Ireland

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Bari, Italy

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Milan, Italy

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Roma, Italy

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Belfast, United Kingdom

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Birmingham, United Kingdom

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Cardiff, United Kingdom

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Glasgow, United Kingdom

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Leeds, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Newcastle, United Kingdom

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Southampton, United Kingdom

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Related Publications (1)

• McKone EF, DiMango EA, Sutharsan S, Barto TL, Campbell D, Ahluwalia N, Higgins M, Owen CA, Tullis E. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021 Mar;20(2):234-242. doi: 10.1016/j.jcf.2020.11.003. Epub 2020 Dec 16.

  PMID: 33339768 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor; tezacaftor, ivacaftor drug combination

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

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: April 8, 2015
• Study Start: June 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: January 8, 2019
• Results First Posted: January 8, 2019

Record last verified: 2019-01

Locations

BE (3); CA (3); IE (2); US (33); IT (3); GB (9); FR (1); DE (8); AU (1)