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VX-659

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Apr 22, 2021

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials4
Total Enrollment788

FDA Designations

No designations recorded

Clinical trial landscape

VX-659 · 4 trials · 1 indication

Phase 3 2Phase 2 1Phase 1 1
NCT03460990A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)Cystic Fibrosis
COMPLETED116 Analytics
NCT03447249A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)Cystic Fibrosis
COMPLETED385 Analytics
PHASE3COMPLETED
A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Cystic FibrosisUnlock trial analytics

Study Endpoints

Primary Endpoints

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline at Week 4

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 (TEAEs) and Serious Adverse Events (SAEs)
Day 1 Through Safety Follow-up (up to Day 61 for Part 1, Day 85 for Part 2 and Day 57 for Part 3)
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
from baseline up to Day 50

Secondary Endpoints

Absolute Change in Sweat Chloride (SwCl)
From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
From Baseline at Week 4
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TEZ/IVAACTIVE_COMPARATORFollowing a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
VX-659/TEZ/IVA TCEXPERIMENTALFollowing a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
PlaceboPLACEBO_COMPARATORParticipants who received placebo matched to VX-659/TEZ/IVA for 24 weeks in the TC treatment period.
Part 1: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-659/TEZ/IVA in TC treatment period for 4 weeks and placebo matched TEZ/IVA in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Low DoseEXPERIMENTALParticipants received VX-659 80 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - Medium DoseEXPERIMENTALParticipants received VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 1: VX-659/TEZ/IVA TC - High DoseEXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 days.
Part 2: TEZ/IVAACTIVE_COMPARATORFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 2: VX-659/TEZ/IVA TCEXPERIMENTALFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-659 400 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in TC treatment period for 4 weeks and TEZ 100 mg qd/IVA 150 mg q12h in washout period for 4 weeks.
Part 3: PlaceboPLACEBO_COMPARATORParticipants received placebo matched to VX-659/TEZ/VX-561 in TC treatment period for 4 weeks.
Part 3: VX-659/TEZ/VX-561 TCEXPERIMENTALParticipants received VX-659 400 mg qd/TEZ 100 mg qd/VX-561 200 mg qd in TC treatment period for 4 weeks.
Part A: VX-659 or Matching PlaceboEXPERIMENTALPart A includes single-dose escalation.
Part B: VX-659 or Matching PlaceboEXPERIMENTALPart B includes multiple-dose escalation.
Part C: VX-659 in TC with TEZ/IVA or Matching Triple PlaceboEXPERIMENTALPart C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
Part D: VX-659 in TC with TEZ/IVA or Matching Triple PlaceboEXPERIMENTALPart D includes subjects with CF. Participants will receive TC or matching placebos.

Interventions

NameTypeDescription
VX-659/TEZ/IVADRUGParticipants received VX-659/TEZ/IVA orally once daily in the morning.
TEZ/IVADRUGParticipants received TEZ/IVA orally once daily in the morning.
IVADRUGParticipants received IVA orally once daily in the evening.
PlaceboDRUGParticipants received placebo matched TEZ/IVA orally once daily in the morning.
VX-659DRUGTablet for oral administration.
Placebo (matched to VX-659/TEZ/IVA)DRUGPlacebo matched to VX-659 and TEZ/IVA.
TEZDRUGTablet for oral administration.
VX-561DRUGTablet for oral administration.
Placebo (matched to VX-659/TEZ/VX-561)DRUGPlacebo matched to VX-659, TEZ and VX-561.
TezacaftorDRUG -
IvacaftorDRUG -
VX-659 Matching PlaceboDRUG -
Triple Combination (TC) Matching PlacebosDRUG -
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Eligibility Criteria

Age Range12 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites46

Key Inclusion Criteria: * Homozygous for the F508del mutation (F/F) * Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: * Clinically significant cirrhosis with or without portal hypertension * Lung infection with org...

Countries:United StatesAustraliaGermanyIrelandSpainUnited KingdomCanadaDenmarkIsraelPolandSwitzerland
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Frequently asked questions about VX-659

What is VX-659 used for?

VX-659 is an investigational small molecule being developed for the treatment of cystic fibrosis. It is being studied in combination therapy for patients with cystic fibrosis, including those who are heterozygous for the F508del mutation and a minimal function mutation, and those who are homozygous for F508del.

Who makes VX-659?

VX-659 is being developed by Vertex Pharmaceuticals Incorporated, a biopharmaceutical company traded on the NASDAQ under the ticker symbol VRTX. Vertex is conducting clinical trials to evaluate the safety and efficacy of VX-659 in patients with cystic fibrosis.

What phase is VX-659 in?

VX-659 is in Phase 3 clinical development. It has completed Phase 1, Phase 2, and Phase 3 trials, with all four trials completed. The drug is investigational and has not been approved by regulatory authorities.

What clinical trials is VX-659 in?

VX-659 has been studied in four completed clinical trials. These include NCT03029455, a Phase 1 study in healthy subjects and adults with cystic fibrosis; NCT03224351, a Phase 2 study of combination therapy; NCT03447249, a Phase 3 study in patients heterozygous for F508del and a minimal function mutation; and NCT03460990, a Phase 3 study in patients homozygous for F508del.

Is VX-659 the same as other cystic fibrosis drugs?

VX-659 is a distinct investigational compound developed by Vertex Pharmaceuticals. It is being studied as part of combination therapy for cystic fibrosis, but it is not the same as other approved Vertex drugs. No alternative names for VX-659 have been reported.