A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR Mutation

NCT02565914 | Completed Phase 3 Results DMC

• 2 other identifiers: VX14-661-1102014-004827-29
• Study Type: interventional
• Target: 1,131
• Locations: 15 countries
• Sites: 151

Brief Summary

This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 up to Week 100

• Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs

  Day 1 up to Week 100

• Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Day 1 up to Week 196

Secondary Outcomes (34)

• Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

  From Baseline at Study 110 Week 96

• Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set

  From Baseline at Study 110 Week 96

• Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set

  From Baseline at Study 110 Week 96

• Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set

  From Baseline at Study 110 Week 96

• Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

  From Baseline at Study 110 Week 96

Study Arms (1)

TEZ/IVA

EXPERIMENTAL

Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks. Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108,109,112 and 114 were administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks. Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks.

Drug: TEZ/IVA; Drug: IVA

Interventions

TEZ/IVA DRUG

Fixed dose tablet for oral administration.

Also known as: VX-661/VX-770, tezacaftor/ivacaftor

TEZ/IVA

IVA DRUG

Tablet for oral administration.

Also known as: VX-770, ivacaftor

TEZ/IVA

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:

• Part A:
• Participants entering the Treatment Cohort must meet all of the following criteria:
• Elect to enroll in the Treatment Cohort
• Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for participants from NCT02508207.
• Willing to remain on a stable CF regimen through the Safety Follow-up Visit.
• Participants re-enrolling in the Part A Treatment Cohort must meet all of the following criteria:
• Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study.
• Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914.
• Participants entering the Part A Observational Cohort must meet the following criteria:
• \<18 years of age (age on the date of informed consent/assent in the parent study)
• Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or
• Received at least 4 weeks of study drug treatment and completed visits up to the last scheduled visit of the Treatment Period of a parent study (and the Safety Follow up Visit for participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort
• Part B:
• Did not withdraw consent from the parent study or Part A of Study NCT02565914.
• Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914.

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 to the subject.
• Pregnant and nursing females.
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
• History of drug intolerance in the parent study that would pose an additional risk to the subject.
• Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator.

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (154)

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Birmingham, Alabama, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Long Beach, California, United States

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Los Angeles, 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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San Diego, 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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Boise, Idaho, United States

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Chicago, Illinois, United States

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Glenview, Illinois, United States

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Niles, Illinois, United States

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Peoria, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Lexington, Kentucky, United States

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New Orleans, Louisiana, 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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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, 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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Long Branch, New Jersey, United States

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New Brunswick, New Jersey, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Buffalo, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Syracuse, 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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Columbus, 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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Sioux Falls, South Dakota, United States

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Knoxville, Tennessee, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, 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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Seattle, Washington, United States

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Spokane, Washington, United States

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Morgantown, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Chermside, Australia

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Melbourne, Australia

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South Brisbane, Australia

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Westmead, Australia

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Graz, Austria

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Innsbruck, Austria

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Salzburg, Austria

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Brussels, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Halifax, Canada

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Montreal, Canada

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Québec, Canada

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Copenhagen, Denmark

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Benite Cedex, France

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Bordeaux, France

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Bron, France

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Lille, France

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Marseille, France

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Montpellier, France

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Paris, France

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Rennes, France

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Roscoff, France

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Rouen, France

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Berlin, Germany

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Bochum, Germany

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Erlangen, Germany

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Essen, Germany

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Frankfurt, Germany

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Giesen, Germany

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Hannover, Germany

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Heidelberg, Germany

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Jena, Germany

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München, Germany

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Tübingen, Germany

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Würzburg, Germany

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Cork, Ireland

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Dublin, Ireland

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Limerick, Ireland

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Haifa, NAP, Israel

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Haifa, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Tel Litwinsky, Israel

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Ancona, Italy

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Genova, Italy

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Milan, Italy

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Orbassano, Italy

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Palermo, Italy

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Potenza, Italy

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Roma, Italy

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Rome, Italy

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Torino, Italy

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Verona, Italy

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Amsterdam, Netherlands

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Heidelberglaan, Netherlands

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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The Hague, Netherlands

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Barcelona, Spain

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Madrid, Spain

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Sabadell, Spain

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Seville, Spain

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Valencia, Spain

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Gothenburg, Sweden

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Stockholm, Sweden

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Uppsala, Sweden

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Bern, Switzerland

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Zurich, Switzerland

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Leeds, West Yorkshire, United Kingdom

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Belfast, United Kingdom

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Birmingham, United Kingdom

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Exeter, United Kingdom

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Glasgow, United Kingdom

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Leeds, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Newcastle upon Tyne, United Kingdom

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Penarth, United Kingdom

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Sheffield, United Kingdom

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Southampton, United Kingdom

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Stoke-on-Trent, United Kingdom

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Related Publications (1)

• Flume PA, Biner RF, Downey DG, Brown C, Jain M, Fischer R, De Boeck K, Sawicki GS, Chang P, Paz-Diaz H, Rubin JL, Yang Y, Hu X, Pasta DJ, Millar SJ, Campbell D, Wang X, Ahluwalia N, Owen CA, Wainwright CE; VX14-661-110 study group. Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study. Lancet Respir Med. 2021 Jul;9(7):733-746. doi: 10.1016/S2213-2600(20)30510-5. Epub 2021 Feb 10.

  PMID: 33581080 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

tezacaftor, ivacaftor drug combination; 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
• 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: September 18, 2015
• First Posted: October 1, 2015
• Study Start: August 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: December 5, 2022
• Last Updated: September 28, 2023
• Results First Posted: June 16, 2020

Record last verified: 2023-09

Locations

AU (4); ES (5); FR (10); DE (12); IE (3); IL (5); BE (3); IT (10); US (69); CA (5); GB (14); CH (2); DK (1); SE (3); NL (5)