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

• Status: Active, not recruiting
• Trial end date: 2022-01-31
• Target enrollment: 0
• Participant gender: All

Summary

The goal of the study is to compare and evaluate safety and efficacy of tesevatinib 50mg versus placebo in patients with ADPKD.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kadmon Corporation, LLC
• Treatments: XL647

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