Recent Updates
Recently added Catalysts

VX-121/TEZ/D-IVA

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Jul 21, 2026

Success Probability

Subscribe to view

Market & Valuation

Subscribe to view

Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials8
Total Enrollment2,298

FDA Designations

No designations recorded

Clinical trial landscape

VX-121/TEZ/D-IVA · 8 trials · 1 indication

Phase 3 4Phase 2 1Phase 1 3
NCT05444257A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination TherapyCystic Fibrosis
ACTIVE NOT_RECRUITING822 Analytics
NCT05422222Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of AgeCystic Fibrosis
ACTIVE NOT_RECRUITING210 Analytics
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 MutationCystic Fibrosis
COMPLETED597 Analytics
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)Cystic Fibrosis
COMPLETED435 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy
Cystic FibrosisUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
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
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
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)
Cystic FibrosisUnlock trial analytics

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
Unlock Study Endpoints

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.
Unlock Study Design Details

Eligibility Criteria

Age Range12 Years to 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
Unlock Eligibility Criteria

Recent Changes (Last 90 Days)

LOWJul 21, 2026NCT05444257lastUpdatePostDate: changed

Frequently asked questions about VX-121/TEZ/D-IVA

What is VX-121/TEZ/D-IVA used for?

VX-121/TEZ/D-IVA is an investigational small molecule combination therapy being developed for the treatment of cystic fibrosis. It is currently in Phase 3 clinical development and is being studied in patients with cystic fibrosis, including pediatric patients as young as 1 year old.

Who makes VX-121/TEZ/D-IVA?

VX-121/TEZ/D-IVA is being developed by Vertex Pharmaceuticals Incorporated, which trades on the NASDAQ under the ticker symbol VRTX. The company is conducting multiple clinical trials to evaluate the safety and efficacy of this combination therapy for cystic fibrosis.

What phase is VX-121/TEZ/D-IVA in?

VX-121/TEZ/D-IVA is in Phase 3 clinical development for cystic fibrosis. It is an investigational drug and has not been approved by regulatory authorities. The ongoing Phase 3 trials are evaluating its long-term safety and efficacy in patients with cystic fibrosis.

What clinical trials is VX-121/TEZ/D-IVA in?

VX-121/TEZ/D-IVA is being studied in several clinical trials, including NCT05422222, a Phase 3 trial in cystic fibrosis patients aged 1 to 11 years, and NCT05444257, a Phase 3 long-term safety and efficacy study in patients aged 12 years and older. Both trials are active but not recruiting.

Is VX-121/TEZ/D-IVA the same as VX-121/tezacaftor/deutivacaftor?

Yes, VX-121/TEZ/D-IVA is the same as VX-121/tezacaftor/deutivacaftor. The abbreviation TEZ refers to tezacaftor and D-IVA refers to deutivacaftor. This combination therapy is being evaluated in clinical trials for the treatment of cystic fibrosis.