A Phase 3 Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutation

NCT02392234 | Completed Phase 3 Results DMC

• 2 other identifiers: VX14-661-1082014-004788-18
• Study Type: interventional
• Target: 248
• Locations: 11 countries
• Sites: 93

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Average of Week 4 and Week 8

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

  Baseline, Week 4 and Week 8 of each treatment period

Secondary Outcomes (6)

• Absolute Change From Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Average of Week 4 and Week 8

  Baseline, Week 4 and Week 8 of each treatment period

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

  Day 1 up to Week 28

• Relative Change From Study Baseline in ppFEV1 at Average of Week 4 and Week 8

  Baseline, Week 4 and Week 8 of each treatment period

• Absolute Change From Study Baseline in Sweat Chloride at Average of Week 4 and Week 8

  Baseline, Week 4 and Week 8 of each treatment period

• Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661), IVA and IVA Metabolite (M1 IVA) After Administration of VX-661/IVA Combination Therapy

  Pre-morning dose on Week 8 of each treatment period

Study Arms (3)

VX-661/Ivacaftor combination

EXPERIMENTAL

Drug: VX-661/Ivacaftor; Drug: Ivacaftor; Drug: Placebo matched to Ivacaftor

Ivacaftor monotherapy

EXPERIMENTAL

Drug: Ivacaftor; Drug: Placebo matched to VX-661/ ivacaftor

Placebo

PLACEBO COMPARATOR

Drug: Placebo matched to VX-661/ ivacaftor; Drug: Placebo matched to Ivacaftor

Interventions

VX-661/Ivacaftor DRUG

Fixed dose combination tablet, oral use

Also known as: VX-661+VX-770

VX-661/Ivacaftor combination

Ivacaftor DRUG

Tablet, oral use

Also known as: IVA, VX-770

Ivacaftor monotherapy; VX-661/Ivacaftor combination

Placebo matched to VX-661/ ivacaftor DRUG

Fixed dose combination tablet, oral use

Ivacaftor monotherapy; Placebo

Placebo matched to Ivacaftor DRUG

Tablet, oral use

Placebo; VX-661/Ivacaftor combination

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 and a second allele with a CFTR mutation predicted to have residual function
• Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (≥) 40 percent (%) and less than or equal to (≤) 90% of predicted normal for age, sex, and height during screening
• Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
• 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 participant
• An acute upper or lower respiratory infection, pulmonary exacerbation
• History of solid organ or hematological transplantation
• Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor \[VX-809\], and/or ivacaftor) within 30 days of screening
• Pregnant and nursing females
• Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (93)

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Long Beach, California, United States

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Oakland, California, United States

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Palo Alto, California, United States

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Sacramento, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Pensacola, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Park Ridge, Illinois, United States

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Iowa City, Iowa, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Grand Rapids, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Lebanon, New Hampshire, United States

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New York, New York, United States

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Syracuse, New York, United States

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Valhalla, New York, United States

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Chapel Hill, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Toledo, Ohio, 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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Sioux Falls, South Dakota, United States

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Memphis, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Tyler, Texas, United States

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Salt Lake City, Utah, United States

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Norfolk, Virginia, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Milwaukee, Wisconsin, United States

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Adelaide, Australia

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Melbourne, Australia

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South Brisbane, Australia

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Westmead, Australia

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Ghent, Belgium

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Montreal, Canada

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Québec, Canada

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Toronto, Canada

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Vancouver, Canada

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Marseille, Bouches-du-Rhone, France

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Montpellier, Herault, France

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Rennes, Ille Et Vilaine, France

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Lille, Nord, France

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Paris, Paris, France

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Bron, Rhone, France

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Bordeaux, France

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Munich, Bavaria, Germany

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München, Bavaria, Germany

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Hanover, Lower Saxony, Germany

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Essen, North Rhine-Westphalia, Germany

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Jena, Thuringia, Germany

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Berlin, Germany

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Haifa, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Ancona, Italy

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Milan, Italy

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Orbassano, Italy

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Potenza, Italy

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Roma, Italy

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Verona, Italy

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Amsterdam, Netherlands

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Rotterdam, Netherlands

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The Hague, Netherlands

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Utrecht, Netherlands

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Bern, Switzerland

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Sankt Gallen, Switzerland

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Zurich, Switzerland

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Exeter, Devon, United Kingdom

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London, Greater London, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Southampton, Hampshire, United Kingdom

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Liverpool, Lancashire, United Kingdom

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Glasgow, Strathclyde, United Kingdom

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Leeds, West Yorkshire, United Kingdom

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Related Publications (4)

• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

  PMID: 37983082 DERIVED

• Acaster S, Mukuria C, Rowen D, Brazier JE, Wainwright CE, Quon BS, Duckers J, Quittner AL, Lou Y, Sosnay PR, McGarry LJ. Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised. Value Health. 2023 Apr;26(4):567-578. doi: 10.1016/j.jval.2022.12.002. Epub 2022 Dec 9.

  PMID: 36509366 DERIVED

• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

  PMID: 33331662 DERIVED

• Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3.

  PMID: 29099333 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

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: March 12, 2015
• First Posted: March 18, 2015
• Study Start: March 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: June 12, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-05

Locations

US (47); BE (1); GB (7); AU (4); DE (6); FR (7); IT (6); CA (4); IL (4); NL (4); CH (3)