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

NCT ID: NCT02565914

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2022-12-05

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TEZ/IVA

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.

Group Type: EXPERIMENTAL

TEZ/IVA

Intervention Type: DRUG

Fixed dose tablet for oral administration.

IVA

Intervention Type: DRUG

Tablet for oral administration.

Interventions

TEZ/IVA

Fixed dose tablet for oral administration.

Intervention Type: DRUG

IVA

Tablet for oral administration.

Intervention Type: DRUG

Other Intervention Names

VX-661/VX-770; tezacaftor/ivacaftor; VX-770; ivacaftor

Eligibility Criteria

Inclusion Criteria

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.

Participants re enrolling in Part B must meet all of the following criteria:

• Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of participants in Study NCT02565914.
• Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B.
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B.

Part C:

• Did not withdraw consent from Part B of Study NCT02565914.
• Completed study drug treatment during Part B of NCT02565914.
• Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Birmingham, Alabama, United States

Tucson, Arizona, United States

Little Rock, Arkansas, United States

Long Beach, California, United States

Los Angeles, California, United States

Oakland, California, United States

Palo Alto, California, United States

Sacramento, California, United States

San Diego, California, United States

Aurora, Colorado, United States

Denver, Colorado, United States

Gainesville, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Pensacola, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Boise, Idaho, United States

Chicago, Illinois, United States

Glenview, Illinois, United States

Niles, Illinois, United States

Peoria, Illinois, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Lexington, Kentucky, United States

New Orleans, Louisiana, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

Minneapolis, Minnesota, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Lebanon, New Hampshire, United States

Long Branch, New Jersey, United States

New Brunswick, New Jersey, United States

Albuquerque, New Mexico, United States

Albany, New York, United States

Buffalo, New York, United States

New Hyde Park, New York, United States

New York, New York, United States

Rochester, New York, United States

Syracuse, New York, United States

Chapel Hill, North Carolina, United States

Akron, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Toledo, Ohio, United States

Oklahoma City, Oklahoma, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Charleston, South Carolina, United States

Sioux Falls, South Dakota, United States

Knoxville, Tennessee, United States

Memphis, Tennessee, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Tyler, Texas, United States

Salt Lake City, Utah, United States

Seattle, Washington, United States

Spokane, Washington, United States

Morgantown, West Virginia, United States

Milwaukee, Wisconsin, United States

Chermside, , Australia

Melbourne, , Australia

South Brisbane, , Australia

Westmead, , Australia

Graz, , Austria

Innsbruck, , Austria

Salzburg, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Halifax, , Canada

Montreal, , Canada

Québec, , Canada

Copenhagen, , Denmark

Benite Cedex, , France

Bordeaux, , France

Bron, , France

Lille, , France

Marseille, , France

Montpellier, , France

Paris, , France

Rennes, , France

Roscoff, , France

Rouen, , France

Berlin, , Germany

Bochum, , Germany

Erlangen, , Germany

Essen, , Germany

Frankfurt, , Germany

Giesen, , Germany

Hannover, , Germany

Heidelberg, , Germany

Jena, , Germany

München, , Germany

Tübingen, , Germany

Würzburg, , Germany

Cork, , Ireland

Dublin, , Ireland

Limerick, , Ireland

Haifa, NAP, Israel

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Tel Litwinsky, , Israel

Ancona, , Italy

Genova, , Italy

Milan, , Italy

Orbassano, , Italy

Palermo, , Italy

Potenza, , Italy

Roma, , Italy

Rome, , Italy

Torino, , Italy

Verona, , Italy

Amsterdam, , Netherlands

Heidelberglaan, , Netherlands

Nijmegen, , Netherlands

Rotterdam, , Netherlands

The Hague, , Netherlands

Barcelona, , Spain

Madrid, , Spain

Sabadell, , Spain

Seville, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Bern, , Switzerland

Zurich, , Switzerland

Leeds, West Yorkshire, United Kingdom

Belfast, , United Kingdom

Birmingham, , United Kingdom

Exeter, , United Kingdom

Glasgow, , United Kingdom

Leeds, , United Kingdom

Liverpool, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Newcastle upon Tyne, , United Kingdom

Penarth, , United Kingdom

Sheffield, , United Kingdom

Southampton, , United Kingdom

Stoke-on-Trent, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Denmark; France; Germany; Ireland; Israel; Italy; Netherlands; Spain; Sweden; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33581080 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004827-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX14-661-110

Identifier Type: -

Identifier Source: org_study_id