Tesevatinib in Subjects With ADPKD

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 17-004307
    NCT ID: NCT03203642
    Sponsor Protocol Number: KD019-211

About this study

The goal of the study is to compare and evaluate safety and efficacy of tesevatinib 50mg versus placebo in patients with ADPKD.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Confirmed diagnosis of ADPKD based on Ravine’s criteria.
  • Subjects < 30 years of age must have at least 2 cysts (unilateral or bilateral) while subjects ≥ 30 years of age must have at least 2 cysts in each kidney (ie, total ≥ 4 cysts).
  • Cysts must be at least 1 cm in size to be considered.
  • At least 18 years old and no more than 60 years old at the time of consent.
  • 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 criteria (htTKV is calculated using total kidney volume obtained from MRI divided by height in meters):
    •  > 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.
  • Subject has the following laboratory values:
    • Platelets > lower limit of normal (LLN);
    • Hemoglobin > 9 g/dL;
    • Total bilirubin ≤ 1.5 mg/dL;
    • Aspartate aminotransferase < 2.5 × ULN;
    • Alanine aminotransferase < 2.5 × ULN;
    • Prothrombin time/partial thromboplastin time ≤ 1.5 × ULN;
    • International normalized ratio (INR) ≤ 1.5, except those subjects taking warfarin who must have INR ≤ 3;
    • Albumin ≥ LLN;
    • Amylase < 1.5 x ULN;
    • Lipase < 1.5 x ULN;
    • Serum potassium within normal limits;
    • Serum magnesium within normal limits.
  • Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy, bilateral tubal ligation, or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of child bearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression. 
  • Women of childbearing potential must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
  • Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 6 months after their last dose of study drug. Effective birth control includes:
    • intrauterine device plus 1 barrier method;
    • on stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, and transdermal) plus 1 barrier method;
    • 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm);  
    • a vasectomized partner.
  • For male subjects who are sexually active and are partners of premenopausal women: 
    • agreement to use two forms of contraception as in criterion 7 above during the treatment period and for at least 6 months after the last dose of study drug, unless the male subject had a vasectomy.
  • Capable of understanding and complying with the protocol and has signed the informed consent form.

Exclusion Criteria

  • Previous partial or total nephrectomy or a kidney transplant.
  • Tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
  • Congenital absence of 1 kidney and/or need for dialysis or transplantation in the foreseeable future.
  • Moderate hematuria. Subjects with microhematuria may be enrolled, unless microhematuria is suspected to be due to infection or recent cyst rupture. If hematuria is due to cyst rupture, the subject may be rescreened after discussion with the Medical Monitor.
  • Uncontrolled hypertension (systolic blood pressure > 160 mmHg; diastolic blood pressure > 100 mmHg) while receiving antihypertensive therapy.
  • Uncontrolled diabetes mellitus (glycated hemoglobin > 8%).
  • Presence of renal or hepatic calculi (stones) causing symptoms.
  • Received any investigational therapy within 30 days prior to initiation of therapy (Day 1).
  • Received tolvaptan within 30 days prior to initiation of therapy (Day 1).
  • Received active treatment (within 4 weeks of initiation of therapy [Day 1]) for urinary tract infection.
  • History of pancreatitis or known risk factors for pancreatitis.
  • 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. Inclusion of 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;
    • History of ventricular rhythm disturbances;
    • Symptomatic heart failure (per New York Heart Association guidelines), unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to study entry;
    • Has a cardiac pacemaker;
    • History of pericardial effusion or presence of pericardial effusion on screening echocardiogram.
  • Subject is taking any medication known to inhibit the CYP3A4 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. A stable regimen (≥ 4 weeks) of antidepressants of the selective serotonin reuptake inhibitor (SSRI) class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine).
  • Uncontrolled intercurrent illness that would limit compliance with study requirements including, but not limited to ongoing or active infections or psychiatric illness.
  • Subject is pregnant, plans to become pregnant, or nursing.
  • Known to be positive for the human immunodeficiency virus or hepatitis B or C, as indicated by a positive test at screening.
  • Known to be immunocompromised.
  • Documented presence of renal vascular disease resulting in uncontrolled hypertension.
  • Has previously received an EGFR inhibitor (including, but not limited to, erlotinib, gefitinib, osimertinib, afatinib, cetuximab, panitumumab, or an investigational agent). 20. Allergy or hypersensitivity to components of either tesevatinib, matched placebo, or their formulations.
  • Aphakic due to previous cataract surgery or congenital abnormality.
    • Note: The sponsor has the option to exclude a subject from enrollment, if, based upon the subject’s medical history or screening results, it is felt that a subject’s safety may be at risk and/or if the safety data may confound the study results.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ziad El-Zoghby, M.D.

Open for enrollment

Contact information:

Lisa Bungum CCRP

(507)266-4616

Bungum.Lisa2@mayo.edu

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CLS-20361912

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