A Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)

NCT03096080 | Completed Phase 1 FDA Drug

• 1 other identifier: KD019-103
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates safety and tolerability of a single ascending dose of a tesevatinib liquid formulation administered to pediatric subjects with ARPKD.

Conditions

Polycystic Kidney, Autosomal Recessive

Keywords

ARPKD; Autosomal Recessive Polycystic Kidney Disease; Pediatric Polycystic Kidney; Tesevatinib; Polycystic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of the safety and tolerability of a single dose tesevatinib liquid formulation in pediatric participants with ARPKD

  Safety and tolerability endpoints will be measured with the aggregated results of frequency and severity of adverse events and safety assessments (e.g. clinical laboratory tests, physical examinations, vital signs, ECGs, audiology testing, ocular monitoring)

  2 weeks

Secondary Outcomes (4)

• Evaluation of the time to peak of plasma concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.

  3 days

• Evaluation of the plasma maximum concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.

  3 days

• Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-Last hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.

  3 days

• Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-24 hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.

  3 days

Study Arms (3)

Cohort 1

EXPERIMENTAL

Single 0.25 mg/kg dose of tesevatinib

Drug: Tesevatinib

Cohort 2

EXPERIMENTAL

Single 0.50 mg/kg dose of tesevatinib

Drug: Tesevatinib

Cohort 3

EXPERIMENTAL

Single 1.00 mg/kg dose of tesevatinib

Drug: Tesevatinib

Interventions

Tesevatinib DRUG

One dose of the study drug in liquid form

Also known as: KD019

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Clinical diagnosis of ARPKD the presence of bilaterally enlarged echogenic kidneys demonstrating poor corticomedullary differentiation and at least 1 of the following:
• Biliary ductal ectasia on magnetic resonance cholangiography or biliary duct ectasia or dilation on ultrasound
• Absence of renal cysts and/or characteristic imaging findings in both parents
• Signs of congenital periportal hepatic fibrosis as indicated by the presence of hepatosplenomegaly and/or esophageal varices and/or coarse liver echogenicity on ultrasound
• Hepatic periportal fibrosis on liver biopsy
• Pathologic (biopsy or autopsy) or genetic diagnosis of ARPKD in a deceased sibling or a clinical diagnosis of ARPKD in a living affected sibling
• The subject's parents or legal authorized representatives have signed a written informed consent per local regulations prior to screening. Assent, when appropriate, has been obtained from the subject according to institutional guidelines.
• The subject has a Lansky Play-Performance score of ≥ 50. Note: Subjects who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• The subject has the following laboratory values:
• Platelets \> 120,000/mm3
• Hemoglobin \> 9 g/dL
• Total bilirubin ≤ 1.5 mg/dL
• Aspartate aminotransferase (AST) \< 2.5 × upper limit of normal (ULN) for age
• Alanine aminotransferase (ALT) \< 2.5 × ULN for age
• eGFR ≥ 50 mL/min/1.73 m2 as measured by Chronic Kidney Disease in Children (CKiD) equation

You may not qualify if:

• The subject has had a previous partial or total nephrectomy.
• The subject has any known genetic syndrome involving the kidney or liver other than ARPKD.
• The subject has had clinically significant gastrointestinal bleeding during the 6 months prior to enrollment.
• The subject has received any investigational therapy within 30 days prior to the first dose of study drug.
• The subject has a history of pancreatitis, has known risk factors for pancreatitis, or baseline elevations in serum amylase or lipase.
• The subject meets any of the following cardiac criteria:
• 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 sudden cardiac death
• History of congenital prolonged QT syndrome, New York Heart Association class III or IV congestive heart failure
• History of cardiac arrhythmias, stroke, or myocardial infarction
• Has a cardiac pacemaker
• The subject has an abnormal baseline audiogram.
• The subject is taking or has taken any medication known to inhibit the cytochrome P450 (CYP) 3A4 isozyme or any drugs that are strong or moderate CYP3A4 inducers within 14 days prior to Day 1 of study drug.
• The subject is taking or has taken any drugs associated with torsades de pointes or known to prolong the QTc interval, including anti-arrhythmic medications within 2 weeks prior to Day 1 of study drug.
• The subject is receiving systemic anticoagulation.

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (2)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Recessive; Polycystic Kidney Diseases

Interventions

XL647

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 30, 2017
• Study Start: August 24, 2017
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: May 11, 2022

Record last verified: 2022-05

Locations

US (2)