A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: ELX/TEZ/IVA; Drug: VX-121/TEZ/D-IVA; Drug: IVA; Drug: Placebo (matched to ELX/TEZ/IVA); Drug: Placebo (matched to VX-121/TEZ/D-IVA); Drug: Placebo (matched to IVA)

• Registration Number: NCT05076149
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no F508del mutation.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-29
• Study First Submitted QC: 2021-09-29
• Study First Posted: 2021-10-13
• Study Start: 2021-10-27
• Primary Completion: 2023-05-18
• Study Completion: 2023-11-30
• Status Verified: 2024-05
• Results First Submitted: 2024-05-16
• Results First Submitted QC: 2024-05-16
• Last Update Submitted: 2024-05-16
• Results First Posted: 2024-06-13
• Last Update Posted: 2024-06-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 597

Inclusion Criteria

• Participant has one of the following genotypes:

  • Homozygous for F508del;
  • Heterozygous for F508del and a gating (F/G) mutation;
  • Heterozygous for F508del and a residual function (F/RF) mutation;
  • At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA and no F508del mutation

• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving CFTR protein modulator therapy; FEV1 >=40% and <=80% for participants not currently receiving CFTR protein modulator therapy

Key

Exclusion Criteria

• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Pregnant or breast-feeding females

Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ELX/TEZ/IVA	ELX/TEZ/IVA	Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
ELX/TEZ/IVA	IVA	Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
ELX/TEZ/IVA	Placebo (matched to VX-121/TEZ/D-IVA)	Following elexacftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) run-in period of 4 weeks, participants received ELX 200 milligram (mg) once daily (qd) /TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 52 weeks.
VX-121/TEZ/D-IVA	Placebo (matched to ELX/TEZ/IVA)	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
VX-121/TEZ/D-IVA	Placebo (matched to IVA)	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.
VX-121/TEZ/D-IVA	VX-121/TEZ/D-IVA	Following ELX/TEZ/IVA run-in period of 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/D-IVA 250 mg qd in the treatment period for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1second (ppFEV1)	From Baseline Through Week 24	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in Sweat Chloride (SwCl)	From Baseline Through Week 24	Sweat samples were collected using an approved collection device.
Percentage of Participants With SwCl <60 Millimole Per Liter (mmol/L) (Pooled With Data From Study VX20-121-102)	From Baseline Through Week 24	Sweat samples were collected using an approved collection device.
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-102)	From Baseline Through Week 24	Sweat samples were collected using an approved collection device.

Trial Locations

Locations (170)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Banner University of Arizona Medical Center; 🇺🇸 Tucson, Arizona, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

Children's Hospital of Colorado; 🇺🇸 Aurora, Colorado, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Nemours Children's Specialty Care; 🇺🇸 Jacksonville, Florida, United States

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