Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

NCT03691779 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: VX18-445-1062018-001695-38
• Study Type: interventional
• Target: 71
• Locations: 5 countries
• Sites: 21

Brief Summary

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (4)

• Part A: Maximum Observed Plasma Concentration (Cmax) of ELX, TEZ, and IVA

  Part A: Day 15

• Part A: Observed Pre-dose Plasma Concentration (Ctrough) of ELX, TEZ, and IVA

  Part A: Day 15

• Part A: Area Under the Concentration Versus Time Curve From 0 to 24 Hours (AUC0-24h) of ELX, TEZ, and IVA

  Part A: Day 15

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

  Part B: Day 1 Through Safety Follow-up Visit (up to Week 28)

Secondary Outcomes (19)

• Part A: Cmax of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

  Part A: Day 15

• Part A: Ctrough of ELX Metabolite (M23-ELX), TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA)

  Part A: Day 15

• Part A: AUC0-24h of ELX Metabolite (M23-ELX) and TEZ Metabolite (M1-TEZ)

  Part A: Day 15

• Part A: Area Under the Concentration Versus Time Curve From 0 to 6 Hours (AUC0-6h) of IVA Metabolite (M1-IVA)

  Part A: Day 15

• Part A: Safety and Tolerability as Assessed by Number of Participants With TEAEs and SAEs

  Part A: Day 1 Through Safety Follow-up Visit (up to Day 43)

Study Arms (2)

Part A: ELX/TEZ/IVA

EXPERIMENTAL

Participants in Part A received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days.

Drug: ELX/TEZ/IVA; Drug: IVA

Part B: ELX/TEZ/IVA

EXPERIMENTAL

Participants in Part B weighing less than (\<) 30 kilograms (kg) at Day 1 received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing greater than equals to (\>=) 30 kg at Day 1 received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks.

Drug: ELX/TEZ/IVA; Drug: IVA

Interventions

ELX/TEZ/IVA DRUG

Fixed-dose combination tablet orally once daily in the morning.

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

Part A: ELX/TEZ/IVA; Part B: ELX/TEZ/IVA

IVA DRUG

IVA tablet orally once daily in the evening.

Also known as: VX-770, ivacaftor

Part A: ELX/TEZ/IVA; Part B: ELX/TEZ/IVA

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
• Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height.

You may not qualify if:

• Clinically significant cirrhosis with or without portal hypertension
• Lung infection with organisms associated with a more rapid decline in pulmonary status.
• Solid organ or hematological transplantation.

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

Birmingham, United Kingdom

Location

Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital

London, 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

• Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA. A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2021 Jun 15;203(12):1522-1532. doi: 10.1164/rccm.202102-0509OC.

  PMID: 33734030 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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 2, 2018
• Study Start: October 2, 2018
• Primary Completion: August 7, 2020
• Study Completion: August 7, 2020
• Last Updated: October 22, 2021
• Results First Posted: October 22, 2021

Record last verified: 2021-08

Locations

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