Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
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| ClinicalTrials.gov Identifier: NCT03203642 |
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Recruitment Status :
Completed
First Posted : June 29, 2017
Last Update Posted : June 1, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autosomal Dominant Polycystic Kidney ADPKD | Drug: Tesevatinib Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 80 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Double-blind Randomized Parallel Group Study of the Efficacy and Safety of Tesevatinib in Subjects With Autosomal Dominant Polycystic Kidney Disease |
| Actual Study Start Date : | October 12, 2017 |
| Actual Primary Completion Date : | January 25, 2022 |
| Actual Study Completion Date : | January 25, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment Group
50mg tesevatinib administered once daily for up to 24 months.
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Drug: Tesevatinib
A once daily dose of tesevatinib 50 mg in a round tablet form of white to off-white color.
Other Name: KD019 |
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Placebo Comparator: Control Group
Matching placebo administered once daily for up to 24 months.
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Drug: Placebo
A once daily dose of matching placebo. |
- 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.
- 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.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03203642
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| Responsible Party: | Kadmon, a Sanofi Company |
| ClinicalTrials.gov Identifier: | NCT03203642 |
| Other Study ID Numbers: |
ACT17675 KD019-211 ( Other Identifier: Kadmon ) |
| First Posted: | June 29, 2017 Key Record Dates |
| Last Update Posted: | June 1, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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ADPKD Autosomal Dominant Polycystic Kidney Disease Polycystic Kidney |
Tesevatinib Polycystic Kidney Disease PKD |
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Arthrogryposis Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Kidney Diseases Urologic Diseases Joint Diseases Musculoskeletal Diseases Muscular Diseases Musculoskeletal Abnormalities Congenital Abnormalities |
Kidney Diseases, Cystic Abnormalities, Multiple Ciliopathies Genetic Diseases, Inborn XL647 Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |