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Restore CFTR Protein Completed with Results
Study to evaluate VX-121 in adults 18 years and older with cystic fibrosis (Vx-121-101 (VX18-121-101))
This study evaluated the safety, tolerability, and effectiveness of three different doses of the drug VX-121 in triple combination with tezacaftor (TEZ) and VX-561 (deuterated ivacaftor) in people with cystic fibrosis who have two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation. The goal of the study was to select the best dose to take into larger clinical studies to prove safety and effectiveness
This study had two parts. In Part 1, participants who had one copy of the F508del mutation and one minimal function mutation, were randomized to receive once daily VX-121 (5mg, 10mg, or 20mg)/TEZ (100mg)/VX-561 (150mg) or triple placebo for 14 days. In Part 2, participants who had two copies of the F508del mutation and were currently taking TEZ/IVA (Symdeko®) were randomized to receive once daily VX-121 (20mg)/TEZ (100mg)/VX-561 (150mg) or TEZ/IVA alone for 14 days.
Eligibility
See other primary eligibility criteria for more information.
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Age:
18 Years and Older -
Mutation(s):
Two Copies F508del or One Copy F508del -
FEV1% Predicted:
40 to 90%
For more information about the results of this study and where it was conducted, visit ClinicalTrials.gov.
Other Primary Eligibility Criteria
For Part 1: Study participants have one copy of the F508del and one minimal CFTR function mutation that is not responsive to tezacaftor, ivacaftor, or tezacaftor/ivacaftor. For Part 2: Study participants must have two copies of the F508del mutation.
Study Results
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What We Learned:
This study found that all three dose levels of the triple combination VX-121/TEZ/VX-561 were well-tolerated in people with CF who have two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation. When compared with triple placebo or to TEZ/IVA alone, VX-121/TEZ/VX-561 led to improvements in lung function (ppFEV1) and a decrease in sweat chloride, with the most improvement shown with the 20mg VX-121/TEZ/VX-561 dose. This dose will now be studied in larger phase 3 studies planned to begin in the fall of 2021.
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Primary Findings:
Effectiveness:
This study was conducted between May 2019 and December 2019. Part 1 enrolled 58 participants: triple placebo: n=10, 5mg VX-121: n=9, 10mg VX-121: n=19, 20mg VX-121: n=20. Part 2 enrolled 28 participants: TEZ/IVA (active control) n=10, 20mg VX-121: n=18.
The study met the primary efficacy endpoint of the change in lung function from baseline to Day 29, as measured by the absolute change in ppFEV1. In Part 1, the highest improvement in lung function was seen in the 20mg VX-121/TEZ/VX-561 group (9.8%) when compared with triple placebo (1.9%) (p<0.0001). In Part 2, the 20mg VX-121/TEZ/VX-561 group had a 15.9% increase in ppFEV1 compared to the active control group (TEZ/IVA) that had virtually no change in lung function (-0.1%) (p<0.0001).
Significant improvements were also seen in sweat chloride. In Part 1, there was a -49.5 mmol/L decrease in sweat chloride in the 20mg VX-121/TEZ/VX-561 group when compared with triple placebo (+2.3 mmol/L) (p<0.0001). In Part 2, there was a -45.5 mmol/L decrease in the 20mg VX-121/TEZ/VX-561 group when compared with active control (TEZ/IVA) (-2.6 mmol/L) (p<0.0001).
Safety:
VX-121/TEZ/VX-561 was generally well-tolerated.
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Citation:
Lancet 2023;DOI https://doi.org/10.1016/s2213-2600(22)00504-5;11(June(6)):550-562
For current information about the overall development status of this drug, please check the Drug Development Pipeline.
Study Design
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Study Type: ?more info
Clinical trials can be observational or interventional. In an observational study, participants are being observed while receiving routine care. In an interventional study, participants receive one or more treatments (interventions) or a placebo so that researchers can evaluate the effects on the participant’s health.
Interventional -
Randomized Study: ?more info
A clinical trial in which participants are assigned by chance to one of two or more treatment arms.
Yes -
Placebo Controlled: ?more info
A clinical trial in which a drug is studied by giving an inactive substance (a placebo) to one group of participants, while the drug being tested is given to another.
Yes -
Length of Participation:
17 weeks -
Number of Study Visits:
10
Additional Information
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Phase: ?more info
The steps involved in development of new drugs. Phase I focuses on initial safety in people. Phase II studies evaluate safety, correct dose and early signs of drug effect. Phase III studies are the final large studies of safety and drug effectiveness before a drug can be reviewed for approval by the FDA. Phase IV studies evaluate a drug after it has been approved by the FDA.
Phase Two -
Study Sponsor: ?more info
The company or organization that initiates and conducts the study.
Vertex -
Study Drugs:
Eligibility
See other primary eligibility criteria for more information.
-
Age:
18 Years and Older -
Mutation(s):
Two Copies F508del or One Copy F508del -
FEV1% Predicted:
40 to 90%
For more information about the results of this study and where it was conducted, visit ClinicalTrials.gov.
Other Primary Eligibility Criteria
For Part 1: Study participants have one copy of the F508del and one minimal CFTR function mutation that is not responsive to tezacaftor, ivacaftor, or tezacaftor/ivacaftor. For Part 2: Study participants must have two copies of the F508del mutation.
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