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 July 2014 by Kadmon Corporation, LLC
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:
NCT01559363
First received: March 9, 2012
Last updated: July 22, 2014
Last verified: July 2014
  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
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

  • Total Cyst Volume [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Evaluate the annualized percent change from baseline in total cyst volume (TCV) 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: 55
Study Start Date: September 2012
Estimated Primary Completion Date: January 2017 (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
Other Name: XL647
Experimental: Cohort 2
Two 50mg KD019 tablets per day for 28 days and up to 24 months
Drug: KD019
Other Name: XL647
Experimental: Cohort 3
Three 50mg KD019 tablets per day for 28 days and up to 24 months
Drug: KD019
Other Name: XL647
Experimental: Phase 2a
An alternate 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
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.
  • KD019 will be dosed on Monday, Wednesday and Friday of each week. 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.
  • This alternate dosing schedule will be explored to determine if it is more tolerable than daily dosing when used chronically in subjects with ADPKD.
  • All participants receive active KD019 study drug.
  • KD019 is an oral tablet dosed on Monday, Wednesday and Friday every week. 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:   18 Years to 55 Years
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 ≥ 50 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

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.
  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: Fahad Sheckley    310-954-2692    FSheckley@mednet.ucla.edu   
Principal Investigator: Anjay Rastogi, MD         
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: Alaina Thompson    314-362-6898    thompsonal@wusm.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, 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: Sonia Maldonado-Schmidt, RN    414-805-0752    smaldonado@mcw.edu   
Principal Investigator: Ashraf El-Meanawy, MD         
Sponsors and Collaborators
Kadmon Corporation, LLC
  More Information

No publications provided

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: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Multicystic Dysplastic Kidney
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Urogenital Abnormalities
Congenital Abnormalities

ClinicalTrials.gov processed this record on August 21, 2014