Phase 2a Study to Evaluate PRS-080 in Anemic Chronic Kidney Disease Patients

Phase 2a Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Repeated Administrations Over 4 Weeks of the Hepcidin Antagonist PRS-080#022-DP in Anemic Chronic Kidney Disease Patients Undergoing Hemodialysis

Anticalin® proteins are engineered human proteins that are able to bind specific target molecules. The Anticalin PRS-080#022-DP to be investigated in this study is directed against hepcidin and is intended for the treatment of anemia of chronic disease. This pilot Phase 2a study shall investigate the safety, pharmacokinetics and pharmacodynamics of repeated administrations of PRS-080#022-DP in anemic stage 5 chronic kidney disease (CKD) patients undergoing hemodialysis.

This is a multi-center, randomized, double-blind, placebo-controlled, multiple ascending dose, pilot Phase 2a study in anemic stage 5 chronic kidney disease patients requiring hemodialysis. Eligible patients will undergo screening assessments and PRS-080#22-DP will be administered by intravenous infusion. The study will consist of 2 dose cohorts of 4 mg/kg and 8 mg/kg body weight with 6 patients in each cohort. Using a standard 4+2 design, 4 patients in each cohort will be randomized to PRS-080#022-DP and 2 patients in each cohort will be randomized to placebo. The decision to escalate the dose will be based on an interim analysis of clinical and laboratory safety as well on a comparison with pharmacokinetic data. Safety and tolerability, pharmacokinetics, pharmacodynamics as well as potential immunogenicity will be investigated.

Inclusion Criteria:

• Patients with stage 5 CKD having been on hemodialysis for at least 90 days;
• Male and post-menopausal (no menses for at least 12 months without an alternative medical cause) female patients with an age of ≥18 years and with a maximum body weight of 85 kg;
• Patients being on stable erythropoiesis stimulating agent dose for 4 weeks prior to Screening;
• Patients being on stable oral or intravenous iron doses for 4 weeks prior to Screening;
• Mean of 3 Hb values during the screening period, each obtained at least 7 days apart must be ≤10.5 g/dL, with a difference of ≤1.0 g/dL between the lowest and highest value;
• Serum ferritin concentration ≥300 ng/mL;
• Transferrin saturation ≤30%;
• Plasma hepcidin concentration at least 5 nmol/L;
• Screening serum folate and vitamin B12 ≥lower limit of normal Hepcidin 5 - 50 nmol/L;
• Male patients with a female partner of childbearing potential agree to use a medically acceptable method of contraception (e.g., condoms, sexual abstinence, vasectomy), not including the rhythm method for 30 days after administration of the study medication; and
• The patient is legally competent, has been informed of the nature, the scope and the relevance of the study, voluntarily agrees to participation and the study's provisions, and has duly signed the informed consent form (ICF). Patient agrees to comply with the protocol-mandated procedures and visits.

Exclusion Criteria:

• Anemia due to causes other than chronic kidney disease, including hemoglobinopathies, hemolytic anemias, myelodysplasia or malignancy;
• Blood transfusion within 2 months before administration of study medication;
• Previous enrollment in this study;
• Patients treated with PRS-080#022-DP in a previous clinical study;
• Current or previous (within 60 days or 5 half-lives before study medication administration) treatment with another investigational drug and/or medical device or participation in another clinical study;
• Employees of the sponsor or patients who are employees or relatives of the investigator;
• Known allergy to any component of the PRS-080#022-DP formulation;
• Positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-hepatitis C virus Ab), or human immunodeficiency virus (HIV), serology test results not older than 3 months are accepted;
• Planned surgery during the study period;
• Known or suspected active infection;
• Active or chronic gastrointestinal bleeding, or known coagulation disorder;
• Unwilling or unable to comply with the protocol, in the judgment of the investigator;
• Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, apoplexy (sudden circulatory disturbances of an organ or specific region of the body) or coronary artery bypass grafting <3 months prior to Screening;
• Congestive heart failure: New York Heart Association Class III or IV;
• Peripheral arterial disease with necrosis, stage IV (Fontaine) or grade III (category 5 and 6, Rutherford); and
• Any medical condition that in the judgment of the investigator might interfere with study participation or jeopardize patient's safety during the study (e.g., active infection).