Dose finding study for Polysialylated Erythropoietin (PSA-EPO) in Chronic Kidney Disease (CKD) subjects

Anaemia associated with Chronic Kidney Disease (CKD) is due to the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin (EPO), as well as, the shortened lifespan of red blood cells (RBCs), iron and other nutritional deficiencies, infection, and inflammation. The prevalence of anaemia increases with progressive deterioration of renal function, and affects more than 90% of people with end stage renal disease. Anaemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function and exercise capacity, and increased left ventricular hypertrophy and heart failure. Treatment of anaemia reduces morbidity and may improve quality of life (QoL). Erythropoietin Stimulating Agents have been established as an effective treatment for anaemia associated with CKD and have improved the management of anaemia over alternatives such as blood transfusion. The first approved recombinant human erythropoietin, epoetin alfa, is administered 2-3 times/week for maximum efficacy. Darbepoetin alfa, has a longer half life allowing for less frequent dosing. Methoxy-polyethylene glycol-epoetin beta is a pegylated product that can be administered once monthly. PSA-EPO is a polysialylated form of erythropoietin (EPO), which is being developed for the treatment of anaemia of CKD. It is thought that polysialylation might produce an improved form of EPO, requiring a lower frequency of injection, have a slower onset of action than EPO, and potentially avert some of the side effects noted for EPO (e.g., thrombotic cardiovascular events). This is a phase 2, open-label, multi-centre and sequential dose finding trial with up to 6 treatment cohorts of 12 pre-dialysis participants per cohort will enrol between 24 and 90 participants >18 years of age with anaemia secondary to CKD, and not had treatment with an ESA in the prior 10 weeks. Two dose level cohorts are initially planned to be sequentially enrolled. Depending on the observed safety profile and pharmacological response, up to four additional open-label cohorts of 12 participants per cohort may be subsequently added to study additional and/or repeat dose levels of PSA-EPO, as determined by a safety review committee. Each participant will receive an open-label dose of PSA-EPO every 2 weeks in the correction phase, and every 4 weeks once the target haemoglobin level has been achieved, for a total of up to 8 doses. The first cohort will receive a starting dose of 1 microgram/kg body weight administered subcutaneously every two weeks. Each participant who completes the study is expected to participate for at least 17 weeks following the screening and attend weekly visits (unless advised differently by the local principal investigator) during that time.