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Tesevatinib

Phase 2

Autosomal Dominant Polycystic Kidney | Small molecule | Nephrology |Sanofi|Last Updated: Feb 6, 2023

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment80

FDA Designations

No designations recorded

Clinical trial landscape

Tesevatinib · 2 trials · 3 indications

Phase 2 1Phase 1 1
NCT03203642Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKDAutosomal Dominant Polycystic Kidney
COMPLETED80 Analytics
PHASE2COMPLETED
Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
Autosomal Dominant Polycystic KidneyUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 12
Baseline (Day 1), Month 12

htTKV was calculated using total kidney volume (in milliliters) obtained from magnetic resonance imaging (MRI) divided by height (in meters). Least square (LS) mean and standard error (SE) were estimated by using analysis of covariance (ANCOVA) model. Change from Baseline in htTKV at Month 12 was reported in this outcome measure.

Change From Baseline in Height Adjusted Total Kidney Volume at Month 18
Baseline (Day 1), Month 18

htTKV was calculated using total kidney volume (in milliliters) obtained from MRI divided by height (in meters). LS mean and SE were estimated by using ANCOVA model. Change from Baseline in htTKV at Month 18 was reported in this outcome measure.

Change From Baseline in Height Adjusted Total Kidney Volume at Month 24
Baseline (Day 1), Month 24

htTKV was calculated using total kidney volume (in milliliters) obtained from MRI divided by height (in meters). LS mean and SE were estimated by using ANCOVA model. Change from Baseline in htTKV at Month 24 was reported in this outcome measure.

Change From Baseline in Height Adjusted Total Kidney Volume at End of Study
Baseline (Day 1), End of study (anytime up to 26 months)

htTKV was calculated using total kidney volume (in milliliters) obtained from MRI divided by height (in meters). LS mean and SE were estimated by using ANCOVA model. Change from Baseline in htTKV at end of study (i.e., up to 26 months) was reported in this outcome measure.

Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)
From Baseline (Day 1) until 30 days after the last dose of study drug (maximum duration: up to 37 months)

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal product and which did not necessarily had to have a causal relationship with the treatment. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed or worsened or became serious from the first dose (Day 1) of the study drug until 30 days after the last dose of study drug.

Phase 1b: Pharmacokinetics (PK): Plasma Concentrations of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.

Phase 1b: Pharmacokinetics: Plasma Concentrations of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.

Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Cmax was defined as maximum observed plasma concentration.

Phase 1b: Pharmacokinetics: Maximum Observed Plasma Concentration of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Cmax was defined as maximum observed plasma concentration.

Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration (Tmax) of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Tmax was defined as time to reach maximum observed plasma concentration.

Phase 1b: Pharmacokinetics: Time of the Maximum Observed Plasma Concentration of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Tmax was defined as time to reach maximum observed plasma concentration.

Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration (Tlast) of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Tlast was defined as time to reach last quantifiable plasma concentration.

Phase 1b: Pharmacokinetics: Time of the Last Quantifiable Plasma Concentration of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

Tlast was defined as time to reach last quantifiable plasma concentration.

Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-t) of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).

Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).

Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Tesevatinib 100 mg and 150 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.

Phase 1b: Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose of Tesevatinib 50 mg
Pre-dose, 1, 2, 4, 8, and 24 hours post-dose on Day 1 and pre-dose, 1, 2, 4, and 24 hours post-dose on Day 14

AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.

Phase 1b: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of Tesevatinib 100 mg and 500 mg
Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6

Ctrough was the plasma concentration observed at the time immediately before (pre-dose) study drug administration.

Phase 1b: Pharmacokinetics: Trough Plasma Concentrations of Tesevatinib 50 mg
Pre-dose on Days 7, 14, 21, 28 and Months 2, 3, 4, 5 and 6

Ctrough was the plasma concentration observed at the time immediately before study drug administration.

Phase 1b: Maximum Tolerated Dose (MTD) of Tesevatinib
Cycle 1 (Up to 28 days)

The MTD was determined based on dose-limiting toxicities (DLTs) occurring in the first 28 days of study treatment. Any toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was considered as DLT.

Phase 2a: Annualized Percent Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)

eGFR: measures kidney function based on serum creatinine (Scr) and cystatin C (Scys). Annualized change in eGFR was calculated as: percent change from Baseline divided by total duration in days\*365.25. eGFR was estimated using 3 formulas and is reported separately for each formula: 1) 4-variable modification of diet in renal disease (MDRD-4) : Black/African-American males:175\*(Creatinine \[Cr\]\^-1.154)\*(Age\^-0.203)\*1.212, other males:175\*(Cr\^-1.154)\*(Age\^-0.203), females: male equation\*0.742.; 2) cystatin C-based chronic kidney disease (CKD) epidemiology (EPI) (CKD-EPI2012cys) equation: based on Scyc levels, for males if \<=0.8: 133\*(Scys/0.8)\^0.499\*0.996\^age, if \>0.8: 133\*(Scys/0.8)\^-1.238\*0.996\^age; for female: male equation\*0.932., 3) Scr- and Scys-based CKD-EPI (CKD EPI2012Scr-cys) equation: 135\*(Scr/0.9)\^XX\*(Scys/0.8)\^XXX\*0.995\^age\*(× 1.08, if black)- XX and XXX had variable values based on different values of Scr and Scys.

Secondary Endpoints

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
From Baseline (Day 1) up to 30 days post last dose of study drug (i.e., up to 26 months)
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study
Baseline (Day 1), Months 12, 18, 24 and at end of study (i.e., anytime up to 26 months)
Phase 2a: Annualized Percent Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 6, 12, 18, 24 and End of Study
Baseline (Day 1), Months 6, 12, 18, 24 and at end of study (i.e., anytime up to 37 months)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
TesevatinibEXPERIMENTALParticipants received tesevatinib 50 mg tablet orally once daily (QD) for up to 25.3 months.
PlaceboPLACEBO_COMPARATORParticipants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily DosingEXPERIMENTALParticipants received tesevatinib 50 milligrams (mg) tablet orally once daily (QD) for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum duration: up to 36 months).
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily DosingEXPERIMENTALParticipants received tesevatinib 100 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily DosingEXPERIMENTALParticipants received tesevatinib 150 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly DosingEXPERIMENTALParticipants received tesevatinib 150 mg tablet orally bi-weekly in alternative dosing schedules on Monday and Thursday for initial 25 days. After initial 25 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly DosingEXPERIMENTALParticipants received tesevatinib 150 mg tablet orally tri-weekly in alternative dosing schedules on Monday, Wednesday and Friday for initial 26 days. After initial 26 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Phase 2a: Safety in Larger Kidneys (SILK) Cohort: Tesevatinib 50 mg Once Daily DosingEXPERIMENTALParticipants with autosomal dominant polycystic kidney disease (and Baseline estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 35 milliliters per minute per 1.73 square meter (mL/min/1.73 m\^2) and less than or equal to (\<=) 80 mL/min/1.73 m\^2, and height-adjusted total kidney volume (htTKV) \>=1000 mL were enrolled and received tesevatinib 50 mg tablet orally QD for initial 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).

Interventions

NameTypeDescription
TesevatinibDRUGPharmaceutical form: Tablet; Route of administration: orally
PlaceboDRUGPharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally
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Eligibility Criteria

Age Range18 Years to 60 Years
SexALL
Healthy VolunteersNo
Study Sites19

Inclusion Criteria: * ADPKD diagnosis based on Ravine's criteria. * Cysts of at least 1 centimeter. * Estimated glomerular filtration rate greater than or equal to (\>=) 25 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) and less than or equal to (\<=) 90 mL/min/1.73 m\^2, using the ...

Countries:United States
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Frequently asked questions about Tesevatinib

What is Tesevatinib used for?

Tesevatinib is an investigational small molecule being studied for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), a form of polycystic kidney disease. It is in Phase 2 clinical development for this condition, which falls under the therapeutic area of nephrology.

Who is developing Tesevatinib?

Tesevatinib is being developed by Sanofi, a biopharmaceutical company traded on the stock exchange under the ticker symbol SNY. The drug is currently in Phase 2 clinical development for Autosomal Dominant Polycystic Kidney Disease.

What phase is Tesevatinib in?

Tesevatinib is in Phase 2 clinical development for Autosomal Dominant Polycystic Kidney Disease. It is an investigational drug and has not been approved by regulatory authorities. Clinical trials for this condition have been completed, including a Phase 2 study.

What clinical trials has Tesevatinib been in?

Tesevatinib has been studied in clinical trials for Autosomal Dominant Polycystic Kidney Disease. One completed trial is NCT03203642, a Phase 2 study evaluating the efficacy and safety of Tesevatinib in subjects with ADPKD, which enrolled 80 participants in the United States.

Is Tesevatinib the same as KD019?

Yes, Tesevatinib is also known as KD019. A completed clinical trial, NCT01559363, was titled 'A Safety, Pharmacokinetic & Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease' and enrolled 69 participants in the United States.

What is the design of the Tesevatinib Phase 2 trial?

The Phase 2 trial of Tesevatinib, identified as NCT03203642, was a randomized, double-blind, placebo-controlled study. It enrolled 80 participants with Autosomal Dominant Polycystic Kidney Disease in the United States and has been completed.