A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation

NCT03537651 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: VX17-661-1162017-002968-40
• Study Type: interventional
• Target: 130
• Locations: 11 countries
• Sites: 55

Brief Summary

This study evaluates the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

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

  Day 1 up to Week 100

Secondary Outcomes (9)

• Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)

  From Parent Study 115 Baseline at Week 96 (Study 116)

• Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS

  From Parent Study 113B Baseline at Week 96 (Study 116)

• Part A: Absolute Change in Sweat Chloride (SwCl) for 115/116 FAS (TEZ/IVA Group)

  From Parent Study 115 Baseline at Week 96 (Study 116)

• Part A: Absolute Change in SwCl for 113B/116 FAS

  From Parent Study 113B Baseline at Week 96 (Study 116)

• Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)

  From Parent Study 115 Baseline at Week 96 (Study 116)

Study Arms (1)

TEZ/IVA

EXPERIMENTAL

Part A: Participants weighing less than (\<)40 kilograms (kg) at Day 1 received tezacaftor (TEZ) 50 milligrams (mg) once daily (qd)/ivacaftor (IVA) 75 mg every 12 hours (q12h) and the participants weighing greater than or equals to (\>=) 40 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks. Doses were adjusted upward for changes in body weight and/or age. Part B: Participants weighing \<30 kg at Day 1 received TEZ 50 mg qd/IVA 75 mg q12h and the participants weighing \>=30 kg at Day 1 received TEZ 100 mg qd/IVA 150 mg q12h in the treatment period up to 192 weeks. Doses were adjusted upward for changes in body weight and/or age.

Drug: TEZ/IVA; Drug: IVA

Interventions

TEZ/IVA DRUG

Fixed-dose combination 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: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115
• Eligible CFTR Mutation

You may not qualify if:

• Pregnant and nursing females
• History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator
• Ongoing participation in another study with investigational drug

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (55)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours/ Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Johns Hopkins All Children's Hospital Outpatient Care Center

St. Petersburg, Florida, 33701, United States

Location

Center for Advanced Pediatrics

Atlanta, Georgia, 30329, United States

Location

St. Luke's CF Center of Idaho

Boise, Idaho, 83702, United States

Location

Riley Hospital for Children Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital & Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Dartmouth Hitchcock Medical Center

Manchester, New Hampshire, 03756, United States

Location

UBMD Pediatrics/ CF Center of Western New York

Buffalo, New York, 14203, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13202, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Sanford Children's Speciality Clinic

Sioux Falls, South Dakota, 57105, United States

Location

Austin Children's Chest Associates

Austin, Texas, 78723, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Perth Children's Hospital

Nedlands, Australia

Location

John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital

New Lambton, Australia

Location

Lady Cilento Children's Hospital

South Brisbane, Australia

Location

The Children's Hospital at Westmead

Westmead, Australia

Location

Universitair Ziekenhuis Brussel - Campus Jette

Brussels, Belgium

Location

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

British Columbia's Children's Hospital

Vancouver, British Columbia, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

McGill University Health Centre, Glen Site, Montreal Children's Hospital

Montreal, Quebec, Canada

Location

Juliane Marie Center, Rigshopitalet

Copenhagen, Denmark

Location

Groupe Hospitaler Pellegrin, CHU De Bordeaux

Bordeaux, France

Location

Hopital Necker, Enfants Malades

Paris, France

Location

Universitaetsklinkum Koeln, CF-Studienzentrum

Cologne, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Clinic of J.W. Goethe University

Frankfurt, Germany

Location

Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin

Giessen, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitaetsklinikum Jena, Mukoviszidose-Zentrum

Jena, Germany

Location

Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin

Tübingen, Germany

Location

Our Lady's Children's Hospital

Dublin, Ireland

Location

University Hospital Limerick

Limerick, Ireland

Location

Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY

Łomianki, Poland

Location

Inselspital - Universitaetsspital Bern

Bern, Switzerland

Location

Kinderspital Zuerich

Zurich, Switzerland

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (3)

• 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

• Sawicki GS, Chilvers M, McNamara J, Naehrlich L, Saunders C, Sermet-Gaudelus I, Wainwright CE, Ahluwalia N, Campbell D, Harris RS, Paz-Diaz H, Shih JL, Davies JC. A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children >/= 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant. J Cyst Fibros. 2022 Jul;21(4):675-683. doi: 10.1016/j.jcf.2022.02.003. Epub 2022 Feb 18.

  PMID: 35190292 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

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
• Restriction Type: OTHER
• 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: May 15, 2018
• First Posted: May 25, 2018
• Study Start: April 25, 2018
• Primary Completion: October 28, 2020
• Study Completion: September 29, 2023
• Last Updated: April 19, 2024
• Results First Posted: November 26, 2021

Record last verified: 2024-03

Locations

CH (2); CA (3); BE (2); US (28); DK (1); IE (2); DE (7); GB (3); AU (4); FR (2); PL (1)