A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)

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: NCT05033080
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous for F508del and a minimal function mutation (F/MF participants).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-26
• Study First Submitted QC: 2021-08-26
• Study First Posted: 2021-09-02
• Study Start: 2021-09-14
• Primary Completion: 2023-05-12
• Study Completion: 2023-11-21
• Results First Submitted: 2024-05-10
• Results First Submitted QC: 2024-06-07
• Results First Posted: 2024-06-10
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-18
• Last Update Posted: 2024-10-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 435

Inclusion Criteria

• Heterozygous for F508del and a minimal function mutation (F/MF genotype)
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA

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	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.
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.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (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 mmol/L (Pooled With Data From Study VX20-121-103)	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 VX20-121-103)	From Baseline Through Week 24	Sweat samples were collected using an approved collection device.

Trial Locations

Locations (139)

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

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

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Miller Children's Hospital / Long Beach Memorial; 🇺🇸 Long Beach, California, United States

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

Kaiser Permanente; 🇺🇸 Oakland, California, United States

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

University of California San Francisco, Lung Transplant Program; 🇺🇸 San Francisco, California, United States

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

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

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