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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Cystic Fibrosis

Treatments: Drug: IVA; Drug: Placebo (matched to ELX/TEZ/IVA); Drug: Placebo (matched to VX-121/TEZ/D-IVA); Drug: ELX/TEZ/IVA; Drug: VX-121/TEZ/D-IVA; Drug: Placebo (matched to IVA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05076149

2021-000694-85 (EudraCT Number)

VX20-121-103

Details and patient eligibility

About

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.

Enrollment: 597 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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597 participants in 2 patient groups

ELX/TEZ/IVA

Active Comparator group

Description:

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.

Treatment:

Drug: ELX/TEZ/IVA

Drug: Placebo (matched to VX-121/TEZ/D-IVA)

Drug: IVA

VX-121/TEZ/D-IVA

Experimental group

Description:

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.

Treatment:

Drug: Placebo (matched to IVA)

Drug: VX-121/TEZ/D-IVA

Drug: Placebo (matched to ELX/TEZ/IVA)