The present study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of ARA 290 administered intravenously to patients with ESRD.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The study endpoints are safety and tolerability parameters (12-lead ECG,
haematology, blood biochemistry including hs-CRP, adverse events),
pharmacokinetics of ARA 290 (venous blood samples at 3, 6 and 12 min). Blood
sampling for hs-CRP will be performed at the start of each hemodialysis
session. If a reduction in hs-CRP is seen in this study, blood samples that
will be collected in the study may be subjected to additional analyses to
further characterize the anti-inflammatory effects of ARA 290.
Secondary outcome
N/A
Background summary
ARA 290 is an 11-amino acid, linear peptide that is being developed as a tissue
protective peptide. ARA 290 mimics the tissue protective pharmacology of
erythropoietin (EPO) but is not erythropoietic. ARA 290 and related peptides
have been shown to be active in preclinical models of stroke, renal
ischemia-reperfusion, renal and neuronal cisplatinum toxicity, diabetic
neuropathy and retinopathy, sciatic nerve crush injury, wound healing, and in
suppressing the wheal induced by intradermally administered histamine.
Study objective
The present study will investigate the safety, tolerability, pharmacokinetics
and pharmacodynamics of ARA 290 administered intravenously to patients with
ESRD.
Study design
Single-centre, randomized, double-blind, placebo-gecontrolled study with
multiple doses of ARA 290. Both cohorts will consist of 6 adult patients with
ESRD (4 active treatment and 2 placebo). If there is a clear effect (defined
as a decrease in hs-CRP >50% from baseline) dose-escalation will be
reconsidered and will follow only after an extension of the number of patients
that will be dosed with 0.7 mg ARA 290 (in a 1:2 placebo:active fashion) to
unambiguously confirm the effects observed in the first 6 patients.
Intervention
Intravenous administration of ARA 290 or placebo (6 doses).
Study burden and risks
Unexpected adverse reactions.
712 Kitchawan Road
Ossining, New York 10562
US
712 Kitchawan Road
Ossining, New York 10562
US
Listed location countries
Age
Inclusion criteria
• Be able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff;
• Willing to comply with study restrictions;
• Between 18 and 65 years of age (inclusive).
• Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive);
• Diagnosis of clinically stable ESRD, as determined by the investigator;
• Requiring regular dialysis therapy for at least 12 weeks prior to first administration of study agent;
• Receiving treatment with IV or SC erythropoietin receptor agonist for a minimum of 8 weeks prior to administration of study agent, requiring doses to remedy EPO-resistance, with evidence of stable hemoglobin levels;
• Baseline hemoglobin values between 9.0 and 12.0 g/dL (5.6 - 7.5 mmol/L) before entering the study;
• CRP levels of at least 7 mg/L;
• Normal serum folate and vitamin B12 levels at screening;
• Having a creatinine clearance below 15 mL/min (chronic kidney disease stage 5), based on the Cockcroft-Gault equation
Exclusion criteria
• Clinically relevant abnormal history of physical and mental health other than conditions related to chronic kidney disease of patient, as determined by medical history taking (as judged by the investigator);
• Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings other than conditions related to chronic kidney disease of patient (as judged by the investigator);
• Subject has uncontrolled hypertension;
• Subject is unable to refrain from the use of disallowed concomitant medication from one week prior to the first study drug administration until follow-up assessments;
• Subject has a history of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food;
• Subject has a history of syncopal episodes;
• Subjects that received a vaccination or immunization within the last month;
• Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug or more than 4 times per year;
• Subject has undergone major surgery within six months prior to screening;
• Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014838-14-NL |
| CCMO | NL29277.058.09 |