A Safety, Pharmacokinetic & Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease
Polycystic Kidney, Autosomal Dominant
About this trial
This is an interventional treatment trial for Polycystic Kidney, Autosomal Dominant
Eligibility Criteria
Inclusion Criteria:
- The participant had a confirmed diagnosis of ADPKD.
- The participant had a GFR >=35 mL/min/1.73m^2.
- Cysts must be at least 1 centimeter 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 participant had a htTKV >= 1000 mL (htTKV was calculated using total kidney volume obtained from magnetic resonance imaging divided by height in meters).
Exclusion Criteria:
- The participant has had a previous partial or total nephrectomy.
- The participant had tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
- The participant had congenital absence of one kidney and/or need for dialysis.
- Presence of renal or hepatic calculi (stones) causing symptoms.
- The participant had received any investigational therapy within 30 days prior to study entry.
- Active treatment (within 4 weeks of study entry) for urinary tract infection.
- Participant was known to be immunocompromised.
- Participant was pregnant or nursing.
- History of pericardial effusion or presence of pericardial effusion on screening echocardiogram
- Uncontrolled hypertension.
- History of pancreatitis or had known risk factors for pancreatitis.
- Participant had received EGFR inhibitor at any time.
- The participant was aphakic due to previous cataract surgery or congenital anomaly.
Sites / Locations
- UCLA Medical Center
- University of Colorado Denver
- University of Kansas Medical Center
- Beth Israel Deaconess Medical Center
- Mayo Clinic
- Washington University School of Medicine
- New York University School of Medicine
- Cleveland Clinic
- Clinical Advancement Center, PLLC
- University of Virginia - Nephrology Clinical Research Center
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Phase 1b: Cohort 1: Tesevatinib 50 mg Once Daily Dosing
Phase 1b: Cohort 2: Tesevatinib 100 mg Once Daily Dosing
Phase 1b: Cohort 3: Tesevatinib 150 mg Once Daily Dosing
Phase 2a: Cohort 4: Tesevatinib: Bi-weekly Dosing
Phase 2a: Cohort 5: Tesevatinib: Tri-weekly Dosing
Phase 2a: Safety in Larger Kidneys (SILK) Cohort: Tesevatinib 50 mg Once Daily Dosing
Participants received tesevatinib 50 milligrams (mg) tablet orally once daily (QD) for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum duration: up to 36 months).
Participants received tesevatinib 100 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Participants received tesevatinib 150 mg tablet orally QD for 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 36 months).
Participants received tesevatinib 150 mg tablet orally bi-weekly in alternative dosing schedules on Monday and Thursday for initial 25 days. After initial 25 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Participants received tesevatinib 150 mg tablet orally tri-weekly in alternative dosing schedules on Monday, Wednesday and Friday for initial 26 days. After initial 26 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).
Participants with autosomal dominant polycystic kidney disease (and Baseline estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 35 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) and less than or equal to (<=) 80 mL/min/1.73 m^2, and height-adjusted total kidney volume (htTKV) >=1000 mL were enrolled and received tesevatinib 50 mg tablet orally QD for initial 28 days. After initial 28 days treatment, at the investigator's discretion, participants continued to receive tesevatinib for a total of 24 months (since treatment initiation) or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant, or investigator decision (maximum exposure duration: up to 28 months).