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Alyftrek

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Sep 10, 2026

Target and mechanism

ModalitySmall molecule

Also known as VX-121 (Suspension), VX-121

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials12
Total Enrollment2,534

FDA Designations

No designations recorded

Clinical trial landscape

Alyftrek · 12 trials · 1 indication

Phase 3 5Phase 2 1Phase 1 6
NCT05844449Evaluation of Long-Term Safety and Efficacy of Vanzacaftor/Tezacaftor/Deutivacaftor in Cystic Fibrosis Participants 1 Year of Age and OlderCystic Fibrosis
ENROLLING BY_INVITATION174 Analytics
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
PHASE3ENROLLING BY_INVITATION
Evaluation of Long-Term Safety and Efficacy of Vanzacaftor/Tezacaftor/Deutivacaftor in Cystic Fibrosis Participants 1 Year of Age and Older
Cystic FibrosisUnlock trial 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

Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs)
From Baseline up to Week 100
Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs)
From Baseline up to Week 196
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 Concentration (Cmax) of Rosuvastatin in the Absence and Presence of VNZ/TEZ/D-IVA
Day 1 up to Day 23
Area Under the Concentration Time-curve (AUC) of Rosuvastatin in the Absence and Presence of VNZ/TEZ/D-IVA
Day 1 up to Day 23
Flavor Assessment Based on Flavor Profile Method of Descriptive Sensory Analysis per American Society for Testing and Material (ASTM) Approved Sensory Evaluation Method
Periodic Intervals up to 30 minutes post oral administration
Part A: Maximum Observed Plasma Concentration (Cmax) of VNZ, TEZ, and D-IVA
Pre-dose up to 288 hours Post-dose
Part B: Maximum Observed Plasma Concentration (Cmax) of VNZ, TEZ, and D-IVA
Pre-dose up to 384 hours Post-dose
Part A: Area Under the Concentration Versus Time Curve (AUC) of VNZ, TEZ, and D-IVA
Pre-dose up to 288 hours Post-dose
Part B: Area Under the Concentration Versus Time Curve (AUC) of VNZ, TEZ, and D-IVA
Pre-dose up to 384 hours Post-dose
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

Part A (All Cohorts): Absolute Change in Sweat Chloride (SwCl)
From Baseline Through Week 96
Part B: Absolute Change in Sweat Chloride (SwCl)
From Baseline Through Week 192
Part A (Cohort 1): Absolute Change in Percent Predicted Forced Expiratory Volume (ppFEV1)
From Baseline Through Week 100
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
VNZ/TEZ/D-IVAEXPERIMENTALPart A: Participants (Cohort 1: 6 through 11 years of age (inclusive); Cohort 2: 2 through 5 years of age (inclusive) and Cohort 3: 1 to less than (\<) 2 years of age) will receive VNZ/TEZ/D-IVA once daily at doses determined based on their age and weight. The age range is based on date of informed consent in parent study. Part B: Participants in Cohort 1 who meet the eligibility criteria will receive VNZ/TEZ/D-IVA for an additional 96 weeks.
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.
VNZ/TEZ/D-IVA and RosuvastatinEXPERIMENTALRosuvastatin will be administered to participants as a single oral dose on Day 1 and then co-administered with VNZ/TEZ/D-IVA on Day 18.VNZ/TEZ/D-IVA dose will be administered once daily (qd) from Day 5 to Day 22.
Part A: Sequence 1EXPERIMENTALParticipants will receive VNZ/TEZ/D-IVA reference fixed dose combination (FDC) tablet in dosing period 1, then VNZ/TEZ/D-IVA test FDC granules dose level 1 in dosing period 2, and finally VNZ/TEZ/D-IVA test FDC granules dose level 2 in dosing period 3. A washout period of 14 days will be maintained between 3 dosing periods.
Part A: Sequence 2EXPERIMENTALParticipants will receive VNZ/TEZ/D-IVA test FDC granules dose level 1 in dosing period 1, then VNZ/TEZ/D-IVA test FDC granules dose level 2 in dosing period 2, and finally VNZ/TEZ/D-IVA reference FDC tablet in dosing period 3. A washout period of 14 days will be maintained between 3 dosing periods.
Part A: Sequence 3EXPERIMENTALParticipants will receive VNZ/TEZ/D-IVA test FDC granules dose level 2 in dosing period 1, then VNZ/TEZ/D-IVA reference FDC tablet in dosing period 2, and finally VNZ/TEZ/D-IVA test FDC granules dose level 1 in dosing period 3. A washout period of 14 days will be maintained between 3 dosing periods.
Part B: Sequence 1EXPERIMENTALParticipants will receive VNZ/TEZ/D-IVA test FDC granules under fasted condition in dosing period 1, then VNZ/TEZ/D-IVA test FDC granules under fed state in dosing period 2. A washout period of 18 days will be maintained between 2 dosing periods.
Part B: Sequence 2EXPERIMENTALParticipants will receive VNZ/TEZ/D-IVA test FDC granules under fed state in dosing period 1, then VNZ/TEZ/D-IVA test FDC granules under fasted condition in dosing period 2. A washout period of 18 days will be maintained between 2 dosing periods.
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
VNZ/TEZ/D-IVADRUGFixed-dose combination tablets or granules for oral administration.
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.
RosuvastatinDRUGTablet 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 Range1 Year to N/A
SexALL
Healthy VolunteersNo
Study Sites37

Key Inclusion Criteria: Parts A and B: • Participants who have completed study drug treatment in the parent study (VX21-121-105; NCT Number: NCT05422222) Part B: -Meets at least 1 of the following criteria: * Completed study drug treatment in Part A * Had study drug interruption(s) in Part A, b...

Countries:United StatesAustraliaCanadaFranceGermanyNetherlandsNew ZealandSwedenSwitzerlandUnited KingdomAustriaBelgiumCzechiaDenmarkGreeceHungaryIrelandIsraelItalyNorwayPolandPortugalSpain
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Recent Changes (Last 90 Days)

LOWSep 10, 2026NCT05444257lastUpdatePostDate: changed
LOWSep 10, 2026NCT05444257lastUpdatePostDate: changed
LOWJul 21, 2026NCT05444257lastUpdatePostDate: changed