Trial record 1 of 2 for:    polycystic kidney disease and Kadmon
Previous Study | Return to List | Next Study

A Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Kadmon Corporation, LLC
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:
NCT01559363
First received: March 9, 2012
Last updated: June 23, 2016
Last verified: June 2016
  Purpose
The primary objective of this study is to determine the safety, plasma pharmacokinetics, and maximum tolerated dose (MTD) of KD019 when administered to subjects with ADPKD.

Condition Intervention Phase
Polycystic Kidney, Autosomal Dominant
Drug: KD019 (tesevatinib)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease

Resource links provided by NLM:


Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:
  • Safety, Plasma Pharmacokinetics and Maximum Tolerated Dose of KD019 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Phase 1b: Determine the safety, plasma pharmacokinetics and maximum tolerated dose (MTD) of KD019 when administered in subjects with ADPKD

  • Glomerular Filtration Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Phase 2a: Evaluate the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019


Secondary Outcome Measures:
  • Total Kidney Volume [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate the annualized percent change from baseline in total kidney volume (TKV) in subjects with ADPKD treated with KD019

  • Serum Creatinine [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate the annualized change from baseline in the reciprocal of serum creatinine in subjects with ADPKD treated with KD019

  • Safety, Tolerability, and Pharmacokinetics of an Alternative Dosing Schedule [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Evaluate the safety profile, tolerability, and pharmacokinetics in subjects with ADPKD treated with KD019 on an alternative dosing schedule. Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD.


Estimated Enrollment: 120
Study Start Date: September 2012
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
One 50mg KD019 tablet per day for 28 days and up to 24 months
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Cohort 2
Two 50mg KD019 tablets per day for 28 days and up to 24 months
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Cohort 3
Three 50mg KD019 tablets per day for 28 days and up to 24 months
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Phase 2a Monday, Wednesday, Friday
An alternate KD019 dosing schedule of dosing on Monday, Wednesday and Friday of each week for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Phase 2a Monday and Thursday
An alternate KD019 dosing schedule of dosing on Monday and Thursday of each week for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Phase 2a, 50mg
One 50mg KD019 tablet per day for 28 days and up to 24 months
Drug: KD019 (tesevatinib)
Other Name: XL647
Experimental: Phase 2a, 50mg (SILK Cohort)
One 50mg KD019 tablet per day for 28 days and up to 24 months
Drug: KD019 (tesevatinib)
Other Name: XL647

Detailed Description:

Phase 1:

  • Primary purpose is to determine the safety of KD019.
  • Dosing is for 28 days daily. After the 28-day treatment period, subjects will, at the discretion of the investigator, continue to receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision. Subjects may continue beyond 24 months at the discretion of the investigator after consultation with the medical monitor.
  • All participants receive active KD019 study drug.
  • KD019 is an oral once daily tablet. Tablets are 50 mg, 100 mg and 150 mg in strength. Participants will enroll into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b will have their dose increased or decreased to the MTD.
  • Study participants will have MRI of the abdomen (kidneys) at Screening and 6 months thereafter to explore effects of KD019.
  • Echocardiogram will be performed at Screening, Day 28, months 3 and 6 and every 6 months thereafter.

Phase 2:

  • Primary purpose is to compare the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019.
  • Two alternate dosing schedules will be explored to determine if they are more tolerable than daily dosing when used chronically in subjects with ADPKD.
  • Subjects will receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision. Subjects may continue beyond 24 months at the discretion of the investigator after consultation with the sponsor.
  • All participants receive active KD019 study drug.
  • Tablets are 50 mg, 100 mg, and 150 mg in strength.
  • Study participants will have MRI of the abdomen (kidneys) at Screening and Month 6 visit and every 6 months after to explore effects of KD019.
  • Echocardiogram will be performed at Screening, Day 28, and Months 3 and 6 and 6 months thereafter.
  Eligibility

Ages Eligible for Study:   22 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has a confirmed diagnosis of ADPKD.
  • The subject has a GFR ≥ 35 mL/min/1.73 m2.
  • Cysts must be at least 1 cm in size.
  • Adequate bone marrow, kidney, and liver function.
  • Must agree to use two forms of birth control for those of child bearing potential
  • Normal amylase and lipase levels
  • The subject has a htTKV ≥ 1000 mL

Exclusion Criteria:

  • The subject has had a previous partial or total nephrectomy.
  • The subject has tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
  • The subject has congenital absence of one kidney and/or need for dialysis.
  • Presence of renal or hepatic calculi (stones) causing symptoms.
  • The subject has received any investigational therapy within 30 days prior to study entry.
  • Active treatment (within 4 weeks of study entry) for urinary tract infection.
  • Subject is known to be immunocompromised
  • Subject is pregnant or nursing
  • History of pericardial effusion or presence of pericardial effusion on screening echocardiogram
  • Uncontrolled hypertension
  • History of pancreatitis or has known risk factors for pancreatitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559363

Locations
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90025
Contact: Tabitha Lin    310-825-7919    tslin@mednet.ucla.edu   
Principal Investigator: Anjay Rastogi, MD         
United States, Kansas
University of Kansas Medical Center Active, not recruiting
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Alice Lee    617-667-0324    alee16@bidmc.harvard.edu   
Principal Investigator: Theodore Steinman, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lisa Bungum    507-266-4616    Bungum.Lisa2@mayo.edu   
Principal Investigator: Ziad El-Zoghby, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Nikki Bauer    314-362-7406    nikkibauer@wustl.edu   
Principal Investigator: Seth Goldberg, MD         
United States, New York
New York University School of Medicine Terminated
New York, New York, United States, 10016
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Kim MacKay    216-444-4650    MACKAYK@ccf.org   
Principal Investigator: Saul Nurko, MD         
United States, Texas
Clinical Advancement Center, PLLC Recruiting
San Antonio, Texas, United States, 78215
Contact: Letti Hudson, RN    210-223-4444      
Principal Investigator: Pablo Pergola, MD         
United States, Virginia
University of Virginia - Nephrology Clinical Research Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Lisa Johnson, BA, CCRC    434-982-3198    SFJ8N@hscmail.mcc.virginia.edu   
Principal Investigator: Mitchell Rosner, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Charlotte Klis    414-805-7183    cklis@mcw.edu   
Principal Investigator: Ashraf El-Meanawy, MD         
Sponsors and Collaborators
Kadmon Corporation, LLC
  More Information

Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT01559363     History of Changes
Other Study ID Numbers: KD019-101 
Study First Received: March 9, 2012
Last Updated: June 23, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic

ClinicalTrials.gov processed this record on July 21, 2016