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Phase 3 Completed N=398 Randomized Quadruple-blind Treatment

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)

Source: ClinicalTrials.gov NCT05033080 ↗
Enrolled (actual)
398
Serious AEs
17.3%
Results posted
Jun 2024
Primary outcomePrimary: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) — 0.3; 0.5 percentage points — p=< 0.0001
◆ Published Evidence
Established
91citations · ~91 / year
Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.
The Lancet. Respiratory medicine · 2025 · Open access · Likely link

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).

Linked Publications (2)

  • Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.
    The Lancet. Respiratory medicine · 2025 · 91 citations · Open access · Likely link
  • Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).
    The Cochrane database of systematic reviews · 2023 · 22 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
0.3; 0.5 < 0.0001 sig
SECONDARY
Absolute Change in Sweat Chloride (SwCl)
0.9; -7.5 < 0.0001 sig
SECONDARY
Percentage of Participants With SwCl <60 mmol/L (Pooled With Data From Study VX20-121-103)
76.6; 85.8 < 0.0001 sig
SECONDARY
Percentage of Participants With SwCl <30 mmol/L (Pooled With Data From Study VX20-121-103)
22.5; 30.5 < 0.0001 sig

Eligibility Criteria

Key Inclusion Criteria

  • Heterozygous for F508del and a minimal function mutation (F/MF genotype)
  • Forced expiratory volume in 1 second (FEV1) value >=40% and =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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05033080) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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