Clinical trial NCT03203642: Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
Official title: A Double-blind Randomized Parallel Group Study of the Efficacy and Safety of Tesevatinib in Subjects With Autosomal Dominant Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autosomal Dominant Polycystic Kidney
ADPKD
Keywords: ADPKD
Autosomal Dominant Polycystic Kidney Disease
Polycystic Kidney
Tesevatinib
Polycystic Kidney Disease
PKD
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-06-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of the study was to compare and evaluate safety and efficacy of tesevatinib 50 milligrams (mg) versus placebo in participants with autosomal dominant polycystic kidney disease (ADPKD).

Detailed description: Safety and efficacy of 50 mg tesevatinib in comparison to placebo in participants with ADPKD was assessed.

The primary purpose of this study was 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, and 30 days post-dose in participants with ADPKD treated with tesevatinib or placebo.

If eligible for the study participation, participants were randomly assigned to either investigational treatment group or placebo group. Treatment group received 50 mg tesevatinib once daily for 24 months and control group received the placebo once daily for 24 months.

Eligibility criteria: Inclusion Criteria:

* ADPKD diagnosis based on Ravine's criteria.
* Cysts of at least 1 centimeter.
* Estimated glomerular filtration rate greater than or equal to (\>=) 25 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) and less than or equal to (\<=) 90 mL/min/1.73 m\^2, using the Modification of Diet in Renal Disease-4 variable formula.
* htTKV must meet the following requirements: \>= 500 milliliters (mL) for participants 18-35 years of age; \>= 750 mL for participants 36-49 years of age; \>= 900 mL for participants 50-60 years of age.
* The participant had the following laboratory values:

Platelets greater than (\>) lower limit of normal (LLN); Hemoglobin \> 9 grams per deciliter; Total bilirubin \<= 1.5 milligrams per deciliter; Aspartate aminotransferase less than (\<) 2.5\*upper limit of normal (ULN); Alanine aminotransferase \< 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\*ULN; Lipase \<=1.5\*ULN; Prothrombin time and partial thromboplastin time \<=1.5\*ULN; International normalized ratio (INR) \<=1.5, except those participants taking warfarin who must have INR \<=3.

* Female participants of childbearing potential with negative pregnancy test at screening.
* If sexually active, the participant agreed 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 participant met any of the following cardiac criteria:
* Mean QTc interval corrected for heart rate using Fridericia's formula (QTcF) of \>450 milliseconds.
* History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (\< 50 beats per minute), 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 electrocardiogram.
* Participants with a history of atrial arrhythmias were 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.
* Participant was pregnant, planed to become pregnant, or nursing.
* Human immunodeficiency virus 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.
* Been aphakic due to previous cataract surgery or congenital abnormality.

Primary outcomes:
measure: Change From Baseline in Height Adjusted Total Kidney Volume (htTKV) at Month 12
timeFrame: Baseline (Day 1), Month 12
measure: Change From Baseline in Height Adjusted Total Kidney Volume at Month 18
timeFrame: Baseline (Day 1), Month 18
measure: Change From Baseline in Height Adjusted Total Kidney Volume at Month 24
timeFrame: Baseline (Day 1), Month 24
measure: Change From Baseline in Height Adjusted Total Kidney Volume at End of Study
timeFrame: Baseline (Day 1), End of study (anytime up to 26 months)
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From Baseline (Day 1) up to 30 days post last dose of study drug (i.e., up to 26 months)
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 18, 24 and End of Study
timeFrame: Baseline (Day 1), Months 12, 18, 24 and at end of study (i.e., anytime up to 26 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: La Mesa
country: United States
facility: California Institute for Renal Research
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale Nephrology Clinical Research
state: Connecticut
city: Port Charlotte
country: United States
facility: Coastal Nephrology Associates Research Center, LLC
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Rogosin Institute
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Temple
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: