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

• ClinicalTrials.gov Identifier: NCT03203642
• Recruitment Status: Recruiting
• First Posted: June 29, 2017
• Last Update Posted: October 31, 2019
• Sponsor: Kadmon Corporation, LLC
• Information provided by (Responsible Party): Kadmon Corporation, LLC

Tracking Information

• First Submitted Date: June 26, 2017
• First Posted Date: June 29, 2017
• Last Update Posted Date: October 31, 2019
• Actual Study Start Date: August 9, 2017
• Estimated Primary Completion Date: August 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 28, 2017)

• Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [ Time Frame: 12 months ]
  Change from baseline of the htTKV will be measured by magnetic resonance imaging (MRI) at Months: 12.
• Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [ Time Frame: 18 month ]
  Change from baseline of the htTKV will be measured by magnetic resonance imaging (MRI) at Months: 18.
• Change of height-adjusted total kidney volume (htTKV) in participants with ADPKD treated with tesevatinib 50mg or placebo. [ Time Frame: 24 month ]
  Change from baseline of the htTKV will be measured by magnetic resonance imaging (MRI) at Months: 24.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03203642 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: June 28, 2017)

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 ]

Incidence of adverse events occurring at the duration of the study will be identified with the following assessments: 12-lead ECGs, ocular evaluations, clinical laboratory tests, echocardiograms, and physical exams.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Autosomal Dominant Polycystic Kidney
• ADPKD

Intervention

• Drug: Tesevatinib
  A once daily dose of tesevatinib 50 mg in a round tablet form of white to off-white color.
  Other Name: KD019
• Drug: Placebo
  A once daily dose of matching placebo.

Study Arms

• Experimental: Treatment Group
  50mg tesevatinib administered once daily for up to 24 months.
  Intervention: Drug: Tesevatinib
• Placebo Comparator: Control Group
  Matching placebo administered once daily for up to 24 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 28, 2017): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 10, 2020
• Estimated Primary Completion Date: August 10, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Director of Clinical Operations; 724-778-6125; KD019-211@kadmon.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03203642
• Other Study ID Numbers: KD019-211
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Kadmon Corporation, LLC
• Study Sponsor: Kadmon Corporation, LLC
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kadmon Corporation, LLC
• Verification Date: October 2019