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

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Brief Title

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

Official Title

A Double-blind Randomized Parallel Group Study of the Efficacy and Safety of Tesevatinib in Subjects With Autosomal Dominant Polycystic Kidney Disease

Brief Summary

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

Detailed Description

      Safety and efficacy of 50mg tesevatinib in comparison to placebo in patients with autosomal
      dominant polycystic kidney disease (ADPKD) will be assessed.

      The primary purpose of this study is focused on evaluating the change from baseline in
      height-adjusted total kidney volume (htTKV) as measured by magnetic resonance imaging (MRI)
      at Months 12, 18, and 24 in patients with ADPKD treated with tesevatinib or placebo.

      If eligible for the study participation, subjects will be randomly assigned to either
      investigational treatment group or placebo group. Treatment group will receive 50mg
      tesevatinib once daily for 24 months and control group will receive the placebo once daily
      for 24 months.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo.

Secondary Outcome

 Safety and Tolerability of tesevatinib 50mg administered once daily in patients with ADPKD measured as incidence of treatment-emergent adverse events.

Condition

Autosomal Dominant Polycystic Kidney

Intervention

Tesevatinib

Study Arms / Comparison Groups

 Treatment Group
Description:  50mg tesevatinib administered once daily for up to 24 months.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

80

Start Date

August 9, 2017

Completion Date

January 31, 2022

Primary Completion Date

January 31, 2022

Eligibility 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
      

Gender

All

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03203642

Organization ID

KD019-211


Responsible Party

Sponsor

Study Sponsor

Kadmon Corporation, LLC


Study Sponsor

, , 


Verification Date

June 2021