Evaluation of Long-term Safety and Efficacy of ELX/TEZ/IVA TC Combination Therapy in Participants With Cystic Fibrosis Who Are 6 Years of Age and Older

NCT04183790 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: VX19-445-1072019-001827-11
• Study Type: interventional
• Target: 64
• Locations: 5 countries
• Sites: 21

Brief Summary

The study evaluates the long-term safety, tolerability, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in participants with cystic fibrosis (CF).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

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

  From Baseline up to Week 196

Secondary Outcomes (12)

• Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

  From Baseline up to Week 192

• Absolute Change in Sweat Chloride (SwCl)

  From Baseline up to Week 192

• Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

  From Baseline up to Week 192

• Absolute Change in Body Mass Index (BMI)

  From Baseline up to Week 192

• Absolute Change in BMI-for-age Z-score

  From Baseline up to Week 192

Study Arms (1)

ELX/TEZ/IVA

EXPERIMENTAL

Participants greater than or equal to (≥) 6 years and less than (\<) 12 years of age and weighing \<30 kilograms (kg) received ELX (elexacaftor) 100 milligram (mg) once daily (qd) /TEZ (tezacaftor) 50 mg qd/IVA (ivacaftor) 75 mg every 12 hours (q12h) and those weighing (≥) 30 kg received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg in the treatment period for up to 192 weeks. Participants ≥12 years of age received ELX 200 mg qd/ TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for up to 192 weeks.

Drug: ELX/TEZ/IVA; Drug: IVA

Interventions

ELX/TEZ/IVA DRUG

Fixed-dose combination (FDC) tablet for oral administration

Also known as: VX-445/VX-661/VX-770, elexacaftor/tezacaftor/ivacaftor

ELX/TEZ/IVA

IVA DRUG

Mono tablet for oral administration.

Also known as: VX-770, ivacaftor

ELX/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 study drug treatment in parent study (VX18-445-106 Part B, NCT03691779), or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study

You may not qualify if:

• History of study drug intolerance in parent study

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (21)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Northwell Health- Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Clinical Research of Charlotte

Charlotte, North Carolina, 28277, United States

Location

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

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Queensland Children's Hospital

South Brisbane, Australia

Location

The Children's Hospital at Westmead

Westmead, Australia

Location

The Hospital for Sick Children

Toronto, Canada

Location

British Columbia's Children's Hospital

Vancouver, Canada

Location

Children's Health Ireland at Crumlin

Dublin, Ireland

Location

Children's Health Ireland at Temple Street

Dublin, Ireland

Location

Birmingham Children's Hospital - NHS Foundation Trust

Birmingham, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, United Kingdom

Location

Related Publications (4)

• Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ramsey B, McKone EF, Tullis E, Mall MA, Taylor-Cousar JL, Waltz D, Ahluwalia N, Chu C, Scirica CV, Davies JC. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children >/=6 Years with Cystic Fibrosis and at Least One F508del Allele: A 192-Week, Phase 3, Open-Label Extension Study. Am J Respir Crit Care Med. 2025 Oct;211(10):1915-1925. doi: 10.1164/rccm.202502-0512OC.

  PMID: 40454869 DERIVED

• 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

• Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ahluwalia N, Chin A, Chu C, Lu M, Menon P, Waltz D, Weinstock T, Zelazoski L, Davies JC. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial. Am J Respir Crit Care Med. 2023 Jul 1;208(1):68-78. doi: 10.1164/rccm.202301-0021OC.

  PMID: 37154609 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

elexacaftor, ivacaftor, tezacaftor 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
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: December 3, 2019
• Study Start: February 17, 2020
• Primary Completion: February 24, 2024
• Study Completion: February 24, 2024
• Last Updated: May 18, 2025
• Results First Posted: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); GB (2); AU (2); US (13); IE (2)