Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD

• Register: ClinicalTrials.gov
• Last refreshed on: 6 June 2022
• Main ID: NCT03203642
• Date of registration: 26/06/2017
• Prospective Registration: Yes
• Primary sponsor: Kadmon, a Sanofi Company
• Public title: Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
• Scientific title: A Double-blind Randomized Parallel Group Study of the Efficacy and Safety of Tesevatinib in Subjects With Autosomal Dominant Polycystic Kidney Disease
• Date of first enrolment: October 12, 2017
• Target sample size: 80
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03203642
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- ADPKD diagnosis based on Ravine's criteria

- Cysts of at least 1 cm

- eGFR = 25 mL/min/1.73 m2 and = 90 mL/min/1.73 m2, using the Modification of Diet in
Renal Disease-4 variable formula

- htTKV must meet the following requirements: = 500 mL for subjects 18-35 years of age;
= 750 mL for subjects 36-49 years of age; = 900 mL for subjects 50-60 years of age

- The subject has the following laboratory values:

Platelets > lower limit of normal (LLN) Hemoglobin > 9 g/dL Total bilirubin = 1.5 mg/dL
Aspartate aminotransferase (AST) < 2.5 × upper limit of normal (ULN) Alanine
aminotransferase (ALT) < 2.5 × ULN Prothrombin time/partial thromboplastin time = 1.5 × ULN
Serum potassium levels within normal limits Serum magnesium levels within normal limits
Albumin = LLN Amylase = 1.5 x ULN Lipase = 1.5 X ULN Prothrombin time (PT) and partial
thromboplastin time (PTT) = 1.5 × ULN International normalized ratio (INR) = 1.5, except
those subjects taking warfarin who must have INR = 3

- Female subjects of childbearing potential with negative pregnancy test at screening

- If sexually active, the subject agrees to use 2 accepted methods of contraception
during the course of the study and for 6 months after their last dose of study drug

Exclusion Criteria:

- Previous nephrectomy

- Kidney transplant

- Tuberous sclerosis

- Hippel-Lindau disease

- Acquired cystic disease

- Congenital absence of 1 kidney and/or need for dialysis or transplantation in the
foreseeable future

- Moderate hematuria

- Uncontrolled hypertension

- Presence of renal or hepatic calculi (stones) causing symptoms

- Received any investigational therapy within 30 days prior to initiation of therapy
(Day 1 visit)

- Received tolvaptan 30 days prior to initiation of therapy (Day 1 visit)

- Received active treatment for urinary tract infection 4 weeks prior to initiation of
therapy (Day 1 visit)

- History of pancreatitis or known risk of pancreatitis

- The subject meets any of the following cardiac criteria:

- Mean QTc interval corrected for heart rate using Fridericia's formula (QTcF) of > 450
msec

- History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic
sinus bradycardia (< 50 bpm), heart block (excluding first-degree block, being PR
interval prolongation only), congenital long QT syndrome or new ST segment elevation
or depression or new Q wave on ECG.

- Subjects with a history of atrial arrhythmias should be discussed with the Medical
Monitor

- Family history of congenital long QT syndrome or unexplained cardiac death

- Symptomatic heart failure (per New York Heart Association guidelines), unstable
angina, myocardial infarction, or cerebrovascular accident within 6 months prior to
study entry

- History of ventricular rhythm disturbances

- History of cardiac arrhythmias, stroke, or myocardial infarction

- Has a cardiac pacemaker

- History of pericardial effusion or presence of pericardial effusion on screening
echocardiogram

- Taking any medication known to inhibit the cytochrome P450 (CYP)3A4 isozyme or any
drugs that are CYP3A4 inducers, or any drugs associated with torsade de pointes or
known to prolong the QTcF interval, including anti-arrhythmic medications within 2
weeks prior to screening

- Uncontrolled intercurrent illness that would limit compliance with study requirements

- Subject is pregnant, plans to become pregnant, or nursing

- HIV positive

- Hepatitis B or C positive

- Immunocompromised

- Documented renal vascular disease resulting in uncontrolled hypertension

- Previously received an epithelial growth factor receptor (EGFR)

- Allergy or hypersensitivity to components of tesevatinib or placebo or their
formulations

- Being aphakic due to previous cataract surgery or congenital abnormality



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

ADPKD

Autosomal Dominant Polycystic Kidney

Intervention(s)

Drug: Placebo

Drug: Tesevatinib

Primary Outcome(s)

Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [Time Frame: 18 month]

Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [Time Frame: 12 months]

Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [Time Frame: 24 month]

Secondary Outcome(s)

Safety and Tolerability of tesevatinib 50mg administered once daily in patients with ADPKD measured as incidence of treatment-emergent adverse events. [Time Frame: 24 months]

Secondary ID(s)

ACT17675

KD019-211

Source(s) of Monetary Support

Please refer to primary and secondary sponsors