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

NCT ID: NCT03203642

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-12
• Study Completion Date: 2022-01-25

Brief Summary

The goal of the study was to compare and evaluate safety and efficacy of tesevatinib 50 milligrams (mg) versus placebo in participants with autosomal dominant polycystic kidney disease (ADPKD).

Detailed Description

Safety and efficacy of 50 mg tesevatinib in comparison to placebo in participants with ADPKD was assessed.

The primary purpose of this study was 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, and 30 days post-dose in participants with ADPKD treated with tesevatinib or placebo.

If eligible for the study participation, participants were randomly assigned to either investigational treatment group or placebo group. Treatment group received 50 mg tesevatinib once daily for 24 months and control group received the placebo once daily for 24 months.

Conditions

Autosomal Dominant Polycystic Kidney; ADPKD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tesevatinib

Participants received tesevatinib 50 mg tablet orally once daily (QD) for up to 25.3 months.

Group Type: EXPERIMENTAL

Tesevatinib

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: orally

Placebo

Participants received placebo matched to tesevatinib tablet orally QD for up to 25.3 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally

Interventions

Tesevatinib

Pharmaceutical form: Tablet; Route of administration: orally

Intervention Type: DRUG

Placebo

Pharmaceutical form: Tablet (identical to tesevatinib); Route of administration: orally

Intervention Type: DRUG

Other Intervention Names

KD019

Eligibility Criteria

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 Modification of Diet in Renal Disease-4 variable formula.
• htTKV must meet the following requirements: >= 500 milliliters (mL) for participants 18-35 years of age; >= 750 mL for participants 36-49 years of age; >= 900 mL for participants 50-60 years of age.
• The participant had the following laboratory values:

Platelets greater than (>) lower limit of normal (LLN); Hemoglobin > 9 grams per deciliter; Total bilirubin <= 1.5 milligrams per deciliter; Aspartate aminotransferase less than (<) 2.5*upper limit of normal (ULN); Alanine aminotransferase < 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*ULN; Lipase <=1.5*ULN; Prothrombin time and partial thromboplastin time <=1.5*ULN; International normalized ratio (INR) <=1.5, except those participants taking warfarin who must have INR <=3.

• Female participants of childbearing potential with negative pregnancy test at screening.
• If sexually active, the participant agreed 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 participant met any of the following cardiac criteria:
• Mean QTc interval corrected for heart rate using Fridericia's formula (QTcF) of >450 milliseconds.
• History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (< 50 beats per minute), 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 electrocardiogram.
• Participants with a history of atrial arrhythmias were 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.
• Participant was pregnant, planed to become pregnant, or nursing.
• Human immunodeficiency virus 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.
• Been aphakic due to previous cataract surgery or congenital abnormality.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kadmon, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California San Diego

La Jolla, California, United States

California Institute for Renal Research

La Mesa, California, United States

University of California Los Angeles

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Yale Nephrology Clinical Research

New Haven, Connecticut, United States

Coastal Nephrology Associates Research Center, LLC

Port Charlotte, Florida, United States

Genesis Clinical Research

Tampa, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University of Maryland

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Rogosin Institute

New York, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor Scott & White Research Institute

Temple, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KD019-211

Identifier Type: OTHER

Identifier Source: secondary_id

ACT17675

Identifier Type: -

Identifier Source: org_study_id