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Tezacaftor

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Apr 19, 2024

Target and mechanism

ModalitySmall molecule

Also known as TEZ

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials8
Total Enrollment1,658

FDA Designations

No designations recorded

Clinical trial landscape

Tezacaftor · 8 trials · 1 indication

Phase 3 5Phase 2 3
NCT03559062A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic FibrosisCystic Fibrosis
COMPLETED67 Analytics
NCT03537651A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR MutationCystic Fibrosis
COMPLETED130 Analytics
NCT03150719A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)Cystic Fibrosis
COMPLETED98 Analytics
NCT02953314A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)Cystic Fibrosis
COMPLETED83 Analytics
NCT02565914A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR MutationCystic Fibrosis
COMPLETED1,131 Analytics
PHASE3COMPLETED
A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic Fibrosis
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Participants With an F508del CFTR Mutation
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate Safety, Efficacy, and Tolerability of TEZ/IVA in Orkambi® (Lumacaftor/Ivacaftor) -Experienced Subjects With Cystic Fibrosis (CF)
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)
Cystic FibrosisUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR Mutation
Cystic FibrosisUnlock trial analytics

Study Endpoints

Primary Endpoints

Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Through Week 8
From baseline through Week 8

LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Day 1 up to Week 100
Incidence of Respiratory Adverse Events of Special Interest (RAESIs)
Day 1 up to Day 84

RAESIs included chest discomfort, dyspnea (shortness of breath), respiration abnormal (chest tightness), asthma, bronchial hyperreactivity, bronchospasm, and wheezing.

Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA
Day 1 and Day 14
Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA
Day 1 and Day 14
Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Day 1 up to Week 28
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Day 1 up to Week 100
Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs
Day 1 up to Week 100
Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Day 1 up to Week 196
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of Study Drug in the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Absolute Change in Total Brody/CF-CT Score
From Baseline at Week 72

The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease.

Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28
Baseline, Day 28

MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.

Secondary Endpoints

Absolute Change in Sweat Chloride At Week 8
From baseline at Week 8
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8
From baseline through Week 8
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit
From first dose of study drug up to safety follow-up visit (up to Week 12)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboOTHERParticipants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks.
TEZ/IVAEXPERIMENTALParticipants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks.
IvacaftorEXPERIMENTALParticipants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks.
Part AEXPERIMENTALParticipants weighing \<25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days. Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days.
Part BEXPERIMENTALParticipants weighing \<40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks. Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks.
Part 1: Placebo - Cohort 1A and 1B CombinedPLACEBO_COMPARATORParticipants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks.
Part 1 Cohort 1A: Triple Combination (TC)EXPERIMENTALParticipants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks.
Part 1 Cohort 1B: TC Low DoseEXPERIMENTALParticipants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks.
Part 1 Cohort 1B: TC High DoseEXPERIMENTALParticipants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks.
Part 2: TEZ/IVAACTIVE_COMPARATORFollowing a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.
Part 2: TC-2EXPERIMENTALFollowing a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.

Interventions

NameTypeDescription
TEZ/IVADRUGParticipants weighing \<40 kg received TEZ 50 mg/IVA 75 mg FDC tablet and those weighing ≥40 kg received TEZ 100 mg/IVA 150 mg FDC tablet.
IVADRUGParticipants weighing \<40 kg IVA 75 mg tablet and those weighing ≥40 kg received IVA 150 mg tablet.
PlaceboDRUGPlacebo matched to TEZ/IVA FDC
Tezacaftor/IvacaftorDRUGTEZ 100 mg/IVA 150 mg fixed-dose combination tablet.
IvacaftorDRUGIVA 150 mg tablet.
TEZDRUG -
VX-440DRUG -
Matched PlaceboDRUG -
Tezacaftor/Ivacaftor matching placeboDRUG -
Ivacaftor matching placeboDRUG -
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Eligibility Criteria

Age Range6 Years to 11 Years
SexALL
Healthy VolunteersNo
Study Sites27

Key Inclusion Criteria: * Homozygous for F508del or heterozygous for F508del and an RF mutation (as defined in the protocol). * Participants with ppFEV1 of ≥70 percentage points adjusted for age, sex, height. * Participants with a screening LCI2.5 result ≥7.5. * Participants who are able to swallow...

Countries:AustraliaBelgiumDenmarkFranceGermanyIrelandPolandSwitzerlandUnited KingdomUnited StatesCanadaAustriaIsraelItalyNetherlandsSpainSweden
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Frequently asked questions about Tezacaftor

What is Tezacaftor/Ivacaftor used for?

Tezacaftor/Ivacaftor is used for the treatment of cystic fibrosis. It is a small molecule combination therapy being developed by Vertex Pharmaceuticals Incorporated. The drug is intended for patients with cystic fibrosis, including those who have previously been treated with Orkambi (lumacaftor/ivacaftor).

How does Tezacaftor/Ivacaftor work?

Tezacaftor/Ivacaftor is a combination of two small molecules that target the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Tezacaftor is a CFTR corrector that helps the protein fold properly, while ivacaftor is a potentiator that enhances channel function. Together, they improve chloride transport in patients with the F508del-CFTR mutation.

Who makes Tezacaftor/Ivacaftor?

Tezacaftor/Ivacaftor is developed by Vertex Pharmaceuticals Incorporated, a biopharmaceutical company traded on the NASDAQ under the ticker symbol VRTX. Vertex is the sole developer of this combination therapy for cystic fibrosis.

What phase is Tezacaftor/Ivacaftor in?

Tezacaftor/Ivacaftor is in Phase 3 clinical development. It has completed three clinical trials, including one Phase 3 study. The drug is investigational and has not been approved by the FDA, as it is still undergoing clinical evaluation for cystic fibrosis.

What clinical trials is Tezacaftor/Ivacaftor in?

Tezacaftor/Ivacaftor has completed three clinical trials. NCT02508207 was a Phase 2 study in the United States with 34 participants. NCT02730208 was a Phase 2 study in Australia with 41 participants. NCT03150719 was a Phase 3 study in the United States, France, and Germany with 98 participants.

Is Tezacaftor/Ivacaftor the same as Orkambi?

Tezacaftor/Ivacaftor is not the same as Orkambi. Orkambi is a combination of lumacaftor and ivacaftor, while Tezacaftor/Ivacaftor combines tezacaftor with ivacaftor. The Phase 3 trial NCT03150719 specifically evaluated Tezacaftor/Ivacaftor in patients who had previously been treated with Orkambi.