Polycystic Kidney, Autosomal RecessivePhase 1NCT03096080
A Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
A Phase 1 study testing Tesevatinib in people with Polycystic Kidney, Autosomal Recessive, run by Kadmon Corporation, LLC at 2 sites in United States.
Trial summary
This study evaluates safety and tolerability of a single ascending dose of a tesevatinib liquid formulation administered to pediatric subjects with ARPKD. Read more about this study
- Who is it for?
- Ages 5 to 12 years
- Conditions the study is for
- Polycystic Kidney, Autosomal Recessive
- What is being tested?
- Tesevatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Aug 2017to 30 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Clinical diagnosis of ARPKD the presence of bilaterally enlarged echogenic kidneys demonstrating poor corticomedullary differentiation and at least 1 of the following:
- Biliary ductal ectasia on magnetic resonance cholangiography or biliary duct ectasia or dilation on ultrasound
- Absence of renal cysts and/or characteristic imaging findings in both parents
- Signs of congenital periportal hepatic fibrosis as indicated by the presence of hepatosplenomegaly and/or esophageal varices and/or coarse liver echogenicity on ultrasound
- Hepatic periportal fibrosis on liver biopsy
- Pathologic (biopsy or autopsy) or genetic diagnosis of ARPKD in a deceased sibling or a clinical diagnosis of ARPKD in a living affected sibling
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- The subject's parents or legal authorized representatives have signed a written informed consent per local regulations prior to screening. Assent, when appropriate, has been obtained from the subject according to institutional guidelines.
- The subject has a Lansky Play-Performance score of ≥ 50. Note: Subjects who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- The subject has the following laboratory values:
- Platelets > 120,000/mm3
- Hemoglobin > 9 g/dL
- Total bilirubin ≤ 1.5 mg/dL
- Aspartate aminotransferase (AST) < 2.5 × upper limit of normal (ULN) for age
- Alanine aminotransferase (ALT) < 2.5 × ULN for age
- eGFR ≥ 50 mL/min/1.73 m2 as measured by Chronic Kidney Disease in Children (CKiD) equation
- Serum potassium levels and serum magnesium levels above the lower limit of normal for age
- Albumin within normal limits for age
- Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 × ULN
- The subject has a normal ejection fraction by echocardiogram.
- The subject has a mean corrected QTcF of ≤ 450 msec.
- The subject has a blood pressure < 95th percentile for age, height, and gender. Subject may be on medication for treatment of hypertension.
- The subject has normal auditory function for age.
- If sexually active, the subject agrees to use 2 accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug.
Who cannot join
- The subject has had a previous partial or total nephrectomy.
- The subject has any known genetic syndrome involving the kidney or liver other than ARPKD.
- The subject has had clinically significant gastrointestinal bleeding during the 6 months prior to enrollment.
- The subject has received any investigational therapy within 30 days prior to the first dose of study drug.
- The subject has a history of pancreatitis, has known risk factors for pancreatitis, or baseline elevations in serum amylase or lipase.
- The subject meets any of the following cardiac criteria:
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- 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 sudden cardiac death
- History of congenital prolonged QT syndrome, New York Heart Association class III or IV congestive heart failure
- History of cardiac arrhythmias, stroke, or myocardial infarction
- Has a cardiac pacemaker
- The subject has an abnormal baseline audiogram.
- The subject is taking or has taken any medication known to inhibit the cytochrome P450 (CYP) 3A4 isozyme or any drugs that are strong or moderate CYP3A4 inducers within 14 days prior to Day 1 of study drug.
- The subject is taking or has taken any drugs associated with torsades de pointes or known to prolong the QTc interval, including anti-arrhythmic medications within 2 weeks prior to Day 1 of study drug.
- The subject is receiving systemic anticoagulation.
- The subject has an uncontrolled intercurrent illness that would limit compliance with study requirements.
- The subject has an uncontrolled infection.
- The subject is known to be positive for the human immunodeficiency virus or hepatitis B or C.
- The subject is known to be immunocompromised.
- The subject has any medical or surgical conditions that would interfere with gastrointestinal absorption of this oral agent.
- The subject has received prior solid organ transplantation.
- The subject, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- The subject has an allergy or hypersensitivity to components of either the tesevatinib or the formulation.
- The subject is aphakic.
- The subject is pregnant or breast feeding.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase 1, Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
This study evaluates safety and tolerability of a single ascending dose of a tesevatinib liquid formulation administered to pediatric subjects with ARPKD.
Read the detailed description
This study is a phase 1 clinical trial focused on evaluating safety and tolerability of the Tesevatinib study drug, which is an oral solution at a 15mg/mL concentration.
To determine safety of the tesevatinib liquid formulation in pediatric subjects (age 5-12) with ARPKD, all participants receive active study drug on Day 1 of the study enrollment. To evaluate plasma pharmacokinetics (PK) of the single dose of tesevatinib in the ARPKD pediatric subjects, the blood for PK sampling is drawn on Day 1, 2, and 3 of the study. Tesevatinib dosing will be followed by a PK and a 2-week safety evaluation. After the completion of the safety review subjects may continue onto the next dosing group at the discretion of the investigator and the medical monitor.
There are three dosing arms in this study. Six participants will enroll into first dosing cohort (0.25mg/kg). Participants may be enrolled in two subsequent cohorts with increased dose (0.5mg/kg and 1.0mg/kg), if safety reporting is favorable.
Medical history will be taken at Screening Visit. Echocardiogram will be performed at Screening and Day 14. Subjects will undergo audiology testing, as well as ocular monitoring at Screening and Day 14. Blood will be drawn for a panel of laboratory tests.
- Conditions
- Polycystic Kidney, Autosomal Recessive
- Being tested
- Tesevatinib
- Keywords
- ARPKD, Autosomal Recessive Polycystic Kidney Disease, Pediatric Polycystic Kidney, Tesevatinib, Polycystic Kidney Disease
- Medical subject headings
- Polycystic Kidney, Autosomal Recessive, Polycystic Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TesevatinibDrug
Also called KD019
One dose of the study drug in liquid form
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Single 0.25 mg/kg dose of tesevatinib Receives: Drug: Tesevatinib |
| Cohort 2 | Experimental | Single 0.50 mg/kg dose of tesevatinib Receives: Drug: Tesevatinib |
| Cohort 3 | Experimental | Single 1.00 mg/kg dose of tesevatinib Receives: Drug: Tesevatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the safety and tolerability of a single dose tesevatinib liquid formulation in pediatric participants with ARPKD
Safety and tolerability endpoints will be measured with the aggregated results of frequency and severity of adverse events and safety assessments (e.g. clinical laboratory tests, physical examinations, vital signs, ECGs, audiology testing, ocular monitoring)
Measured: 2 weeks
Secondary outcomes (4)
Evaluation of the time to peak of plasma concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.
Pharmacokinetic parameter Tmax for tesevatinib will be measured as time elapsed till peak concentration.
Measured: 3 days
Evaluation of the plasma maximum concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.
Pharmacokinetic parameter Cmax for tesevatinib will be used to measure the highest concentration of the drug in plasma.
Measured: 3 days
Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-Last hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.
Pharmacokinetic parameter AUC0-Last for tesevatinib will be measured and summarized by dose.
Measured: 3 days
Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-24 hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.
Pharmacokinetic parameter AUC0-24 for tesevatinib will be measured and summarized by dose.
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2017
- Study start24 Aug 2017
- Primary completion30 Sep 2019
- Study completion30 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Kidney, Autosomal RecessiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kadmon Corporation, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03096080
- Sponsor's protocol ID
- KD019-103
- Status last verified
- May 2022
- First submitted
- 6 Mar 2017
- Last updated
- 11 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
- ClinicalTrials.gov ID
- NCT03096080
- Acronym / sponsor ID
- KD019-103
- Conditions
- Polycystic Kidney, Autosomal Recessive
- Keywords
- ARPKD, Autosomal Recessive Polycystic Kidney Disease, Pediatric Polycystic Kidney, Tesevatinib, Polycystic Kidney Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Kadmon Corporation, LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2017 (actual)
- Primary completion
- 30 Sep 2019 (actual)
- Study completion
- 30 Sep 2019 (actual)
- First posted
- 30 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates safety and tolerability of a single ascending dose of a tesevatinib liquid formulation administered to pediatric subjects with ARPKD.
Detailed description
This study is a phase 1 clinical trial focused on evaluating safety and tolerability of the Tesevatinib study drug, which is an oral solution at a 15mg/mL concentration.
To determine safety of the tesevatinib liquid formulation in pediatric subjects (age 5-12) with ARPKD, all participants receive active study drug on Day 1 of the study enrollment. To evaluate plasma pharmacokinetics (PK) of the single dose of tesevatinib in the ARPKD pediatric subjects, the blood for PK sampling is drawn on Day 1, 2, and 3 of the study. Tesevatinib dosing will be followed by a PK and a 2-week safety evaluation. After the completion of the safety review subjects may continue onto the next dosing group at the discretion of the investigator and the medical monitor.
There are three dosing arms in this study. Six participants will enroll into first dosing cohort (0.25mg/kg). Participants may be enrolled in two subsequent cohorts with increased dose (0.5mg/kg and 1.0mg/kg), if safety reporting is favorable.
Medical history will be taken at Screening Visit. Echocardiogram will be performed at Screening and Day 14. Subjects will undergo audiology testing, as well as ocular monitoring at Screening and Day 14. Blood will be drawn for a panel of laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: TesevatinibSingle 0.25 mg/kg dose of tesevatinib |
| Cohort 2 | Experimental | Drug: TesevatinibSingle 0.50 mg/kg dose of tesevatinib |
| Cohort 3 | Experimental | Drug: TesevatinibSingle 1.00 mg/kg dose of tesevatinib |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (23 listed)
- Clinical diagnosis of ARPKD the presence of bilaterally enlarged echogenic kidneys demonstrating poor corticomedullary differentiation and at least 1 of the following:
- The subject's parents or legal authorized representatives have signed a written informed consent per local regulations prior to screening. Assent, when appropriate, has been obtained from the subject according to institutional guidelines.
- The subject has a Lansky Play-Performance score of ≥ 50. Note: Subjects who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- The subject has the following laboratory values:
- The subject has a normal ejection fraction by echocardiogram.
Key exclusion criteria (25 listed)
- The subject has had a previous partial or total nephrectomy.
- The subject has any known genetic syndrome involving the kidney or liver other than ARPKD.
- The subject has had clinically significant gastrointestinal bleeding during the 6 months prior to enrollment.
- The subject has received any investigational therapy within 30 days prior to the first dose of study drug.
- The subject has a history of pancreatitis, has known risk factors for pancreatitis, or baseline elevations in serum amylase or lipase.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TesevatinibAlso: KD019One dose of the study drug in liquid form | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Evaluation of the safety and tolerability of a single dose tesevatinib liquid formulation in pediatric participants with ARPKD
Time frame: 2 weeks
Safety and tolerability endpoints will be measured with the aggregated results of frequency and severity of adverse events and safety assessments (e.g. clinical laboratory tests, physical examinations, vital signs, ECGs, audiology testing, ocular monitoring)
4 secondary outcomes
Evaluation of the time to peak of plasma concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.
Time frame: 3 days
Evaluation of the plasma maximum concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD.
Time frame: 3 days
Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-Last hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.
Time frame: 3 days
Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-24 hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD.
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tesevatinib in people with Polycystic Kidney, Autosomal Recessive, run by Kadmon Corporation, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the safety and tolerability of a single dose tesevatinib liquid formulation in pediatric participants with ARPKD (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2022.