Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KD019
Tesevatinib · 2 trials · 3 indications
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.
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.
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.
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.
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.
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Plasma concentrations of tesevatinib was analyzed using non-compartmental analysis.
Cmax was defined as maximum observed plasma concentration.
Cmax was defined as maximum observed plasma concentration.
Tmax was defined as time to reach maximum observed plasma concentration.
Tmax was defined as time to reach maximum observed plasma concentration.
Tlast was defined as time to reach last quantifiable plasma concentration.
Tlast was defined as time to reach last quantifiable plasma concentration.
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
AUC0-last was defined as area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (tlast).
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
AUC0-24 was defined as area under the plasma concentration versus time curve of study drug from time 0 to 24 hours post-dose.
Ctrough was the plasma concentration observed at the time immediately before (pre-dose) study drug administration.
Ctrough was the plasma concentration observed at the time immediately before study drug administration.
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.
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.
| Arm | Type | Description |
|---|---|---|
| Tesevatinib | EXPERIMENTAL | Participants received tesevatinib 50 mg tablet orally once daily (QD) for up to 25.3 months. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months. |
| Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing | EXPERIMENTAL | Participants 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 Dosing | EXPERIMENTAL | Participants 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 Dosing | EXPERIMENTAL | Participants 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 Dosing | EXPERIMENTAL | Participants 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 Dosing | EXPERIMENTAL | Participants 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 Dosing | EXPERIMENTAL | Participants 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). |
| Name | Type | Description |
|---|---|---|
| Tesevatinib | DRUG | Pharmaceutical form: Tablet; Route of administration: orally |
| Placebo | DRUG | Pharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally |
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 ...
Tesevatinib is being developed for autosomal dominant polycystic kidney disease, a genetic kidney disorder. It is an investigational small molecule and is not approved for this or any other use. Clinical work in this indication has been conducted by Sanofi.
Tesevatinib targets EPHB4, EGFR, and ERBB2. It is an inhibitor of these proteins. By blocking these targets, the drug is designed to interfere with signaling pathways that contribute to cyst growth and kidney enlargement in autosomal dominant polycystic kidney disease.
Tesevatinib is developed by Sanofi, which trades under the ticker SNY. Sanofi has sponsored the clinical studies of the drug in autosomal dominant polycystic kidney disease conducted in the United States.
Tesevatinib is in Phase 2 development for autosomal dominant polycystic kidney disease. It is investigational and has not been approved by the FDA. Two trials have been completed, and no trials are currently active.
Tesevatinib has been studied in two completed trials. NCT03203642 was a Phase 2 efficacy and safety study in autosomal dominant polycystic kidney disease with 80 participants. NCT01559363 was a Phase 1 safety, pharmacokinetic, and dose-escalation study in the same condition with 69 participants. Both enrolled adults in the United States.
Yes, Tesevatinib is also known as KD019. The Phase 1 trial NCT01559363 was conducted under the KD019 name, while the Phase 2 trial NCT03203642 used the Tesevatinib name. Both refer to the same Sanofi compound being studied in autosomal dominant polycystic kidney disease.