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VX-121/TEZ/D-IVA

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: May 28, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials8
Total Enrollment2,298
FDA Designations
No designations recorded
Clinical Trials (8)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05444257A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination TherapyPHASE3 ACTIVE NOT_RECRUITING 822Nov 8, 2022Oct 30, 2026May 5, 2026195 United States, Australia +21
NCT05422222Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of AgePHASE3 ACTIVE NOT_RECRUITING 210Jun 21, 2022Jun 30, 2030May 28, 202638 United States, Australia +8
NCT05076149A 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 MutationPHASE3 COMPLETED 597Oct 27, 2021Nov 30, 2023Jun 13, 2024170 United States, Australia +18
NCT05033080A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)PHASE3 COMPLETED 435Sep 14, 2021Nov 21, 2023Oct 3, 2024139 United States, Australia +10
NCT03912233A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic FibrosisPHASE2 COMPLETED 87Apr 30, 2019Dec 10, 2019Apr 20, 202326 United States, Germany +3
NCT05535959A Study to Evaluate the Relative Bioavailability of a Fixed-dose Combination Tablet of VX-121/Tezacaftor/DeutivacaftorPHASE1 COMPLETED 16Sep 15, 2022Nov 9, 2022Dec 12, 20221 United States
NCT05437120Pharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic ImpairmentPHASE1 COMPLETED 16Jul 22, 2022Mar 16, 2023Mar 30, 20232 United States
NCT03768089Study of VX-121 in Healthy Subjects and in Subjects With Cystic FibrosisPHASE1 COMPLETED 115Mar 20, 2018May 3, 2019Jul 14, 20227 Netherlands, United Kingdom
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Study Endpoints
Primary Endpoints
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From Baseline up to Week 148
Part A: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites
From Day 1 up to Day 22
Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From Day 1 up to Day 50
Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From Day 1 up to Week 28
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.

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.

Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, and D-IVA
Pre-dose up to 288 hours Post-dose
Area Under the Concentration Versus Time Curve (AUC) of VX-121, TEZ, and D-IVA
Pre-dose up to 288 hours Post-dose
Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant Metabolites
Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-dose up to Day 13
Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant Metabolites
Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-Dose up to Day 13
Fraction Unbound (fu) for VX-121 and D-IVA in Plasma
Cohorts 1 and 2: Pre-dose up to Day 2
Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA
Cohorts 1 and 2: Pre-dose up to Day 2
Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVA
Cohorts 1 and 2: Pre-dose up to Day 2
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)
Secondary Endpoints
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline up to Week 144
Absolute Change From Baseline in Sweat Chloride (SwCl)
From Baseline up to Week 144
Number of Pulmonary Exacerbations (PEx)
From Baseline up to Week 144
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
VX-121/TEZ/D-IVAEXPERIMENTALPart A: Participants will receive VX-121/TEZ/D-IVA once daily for 96 weeks. Part B: Participants will receive VX-121/TEZ/D-IVA once daily for an additional 48 weeks.
Part A: VX-121/TEZ/D-IVAEXPERIMENTALParticipants will receive VX-121/TEZ/D-IVA in the morning.
Part B: VX-121/TEZ/D-IVAEXPERIMENTALParticipants will receive VX-121/TEZ/D-IVA in the morning with the dose(s) to be based on the outcome of Part A.
ELX/TEZ/IVAACTIVE_COMPARATORFollowing 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.
Part 1: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
Part 1: VX-121/TEZ/VX-561 TC - Low DoseEXPERIMENTALParticipants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
Part 1: VX-121/TEZ/VX-561 TC - Medium DoseEXPERIMENTALParticipants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Part 1: VX-121/TEZ/VX-561 TC - High DoseEXPERIMENTALParticipants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Part 2: TEZ/IVAACTIVE_COMPARATORFollowing run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.
Part 2: VX-121/TEZ/VX-561 TC - High DoseEXPERIMENTALFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
Sequence 1EXPERIMENTALParticipants will receive a single dose of reference FDC tablet of VX-121/TEZ/D-IVA in dosing period 1, followed by a single dose of test FDC tablet of VX-121/TEZ/D-IVA in dosing period 2. A washout period of 14 days will be maintained between the 2 dosing periods.
Sequence 2EXPERIMENTALParticipants will receive a single dose of test FDC tablet of VX-121/TEZ/D-IVA in dosing period 1, followed by a single dose of reference FDC tablet of VX-121/TEZ/D-IVA in dosing period 2. A washout period of 14 days will be maintained between the 2 dosing periods.
Cohort 1: Moderate Hepatic ImpairmentEXPERIMENTALParticipants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA .
Cohort 2: Matched Healthy ParticipantsEXPERIMENTALHealthy participants will receive single dose of VX-121/TEZ/D-IVA.
Part A: Pooled Placebo (Cohorts A1-5; Except A3)PLACEBO_COMPARATORParticipants received single dose of placebo matched to VX-121.
Part A: VX-121 (Cohort A1)EXPERIMENTALParticipants received single dose of VX-121 10 milligrams (mg).
Part A: VX-121 (Cohort A2)EXPERIMENTALParticipants received single dose of VX-121 20 mg.
Part A: VX-121 (Cohort A3)EXPERIMENTALParticipants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
Part A: VX-121 (Cohort A4)EXPERIMENTALParticipants received single dose of VX-121 40 mg.
Part A: VX-121 (Cohort A5)EXPERIMENTALParticipants received single dose of VX-121 60 mg.
Part A: VX-121 (Cohort A9)EXPERIMENTALParticipants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.
Part B: Pooled Placebo (Cohorts B1-4)PLACEBO_COMPARATORParticipants received placebo matched to VX-121 for 10 days.
Part B: VX-121 (Cohort B1)EXPERIMENTALParticipants received VX-121 10 mg once daily (qd) for 10 days.
Part B: VX-121 (Cohort B2)EXPERIMENTALParticipants received VX-121 20 mg qd for 10 days.
Part B: VX-121 (Cohort B3)EXPERIMENTALParticipants received VX-121 40 mg qd for 10 days.
Part B: VX-121 (Cohort B4)EXPERIMENTALParticipants received VX-121 60 mg qd for 10 days.
Part C: Pooled Placebo (Cohorts C1-3)PLACEBO_COMPARATORParticipants received placebo matched to VX-121/TEZ/IVA for 14 days.
Part C: VX-121 (Cohort C1)EXPERIMENTALParticipants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
Part C: VX-121 (Cohort C2)EXPERIMENTALParticipants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part C: VX-121 (Cohort C3)EXPERIMENTALParticipants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part D: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
Part D: VX-121/TEZ/IVAEXPERIMENTALParticipants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
Interventions
NameTypeDescription
VX-121/TEZ/D-IVADRUGFixed-dose combination tablets for oral administration.
ELX/TEZ/IVADRUGFixed-dose combination tablets for oral administration.
IVADRUGTablet for oral administration.
Placebo (matched to VX-121/TEZ/D-IVA)DRUGPlacebo matched to VX-121/TEZ/D-IVA for oral administration.
Placebo (matched to ELX/TEZ/IVA)DRUGPlacebo matched to ELX/TEZ/IVA for oral administration.
Placebo (matched to IVA)DRUGPlacebo matched to IVA for oral administration.
VX-121DRUGTablets for oral administration.
TEZDRUGTEZ tablet for oral administration.
VX-561DRUGTablets for oral administration.
TEZ/IVADRUGFixed-dose combination tablets for oral administration.
PlaceboDRUGPlacebos matched to VX-121, TEZ, and VX-561 for oral administration.
Placebo (matched to VX-121 suspension)DRUGPlacebo matched to VX-121 suspension for oral administration.
VX-121 (Suspension)DRUGSuspension for oral administration.
Placebo (matched to TEZ/IVA)DRUGPlacebo matched to TEZ/IVA for oral administration.
VX-121 (Tablet)DRUGTablet for oral administration.
Placebo (matched to VX-121 tablet)DRUGPlacebo matched to VX-121 tablet for oral administration.
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Eligibility Criteria
Age Range12 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites195

Key Inclusion Criteria: * Part A: Completed study drug treatment in a parent study VX20-121-102 (NCT05033080) and VX20-121-103 (NCT05076149); or had study drug interruption(s) in a parent study but did not permanently discontinue study drug, and completed study visits up to the last scheduled visit...

Countries:United StatesAustraliaAustriaBelgiumCanadaCzechiaDenmarkFranceGermanyGreeceHungaryIrelandIsraelItalyNetherlandsNew ZealandNorwayPolandPortugalSpainSwedenSwitzerlandUnited Kingdom
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Recent Changes (Last 90 Days)
MEDIUMMay 29, 2026NCT05422222Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMMay 29, 2026NCT05422222Status: RECRUITING → ACTIVE_NOT_RECRUITING
MEDIUMMay 29, 2026NCT05422222Status: RECRUITING → ACTIVE_NOT_RECRUITING
LOWMay 26, 2026NCT05422222primaryCompletionDate: changed
LOWMay 26, 2026NCT05444257primaryCompletionDate: changed
LOWMay 24, 2026NCT05422222studyFirstPostDate: changed
LOWMay 24, 2026NCT05444257studyFirstPostDate: changed