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

Study Overview
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Brief Summary
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Anticalins® 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 Phase Ib study shall investigate the safety, pharmacokinetics and pharmacodynamics of a single administration of PRS-080#022-DP in anemic stage 5 chronic kidney disease patients undergoing hemodialysis.

Detailed Description
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This is a multi-center, randomized, double-blind, placebo-controlled, single ascending dose phase Ib study in anemic stage 5 chronic kidney disease patients requiring hemodialysis. Eligible subjects will undergo screening assessments and PRS-080#22-DP will be administered by intravenous infusion. The study will consist of 3 dose cohorts of 2 mg/kg, 4 mg/kg, and 8 mg/kg body weight with 8 subjects in each cohort. Using a standard 6+2 design, 6 subjects in each cohort will be randomized to PRS-080#022-DP and 2 subjects in each cohort will be randomized to placebo. The decision to escalate the dose will be based on an interim analysis of clinical safety and safety laboratory data. Safety and tolerability, pharmacokinetics, pharmacodynamics as well as potential immunogenicity will be investigated.

Official Title
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Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Hepcidin Antagonist PRS-080#022-DP in Anemic Chronic Kidney Disease Patients Undergoing Hemodialysis

Conditions
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Anemia of Chronic Kidney Disease

Intervention / Treatment
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* Biological: PRS-080#022-DP
* Biological: PRS-080-Placebo#001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with stage 5 chronic kidney disease having been on hemodialysis for at least 90 days Patients being on stable erythropoiesis-stimulating agent (ESA) dose Hemoglobin (Hb) 9 - 11 g/dL Ferritin ≥ 300 ng/mL. Transferrin saturation (TSAT) ≤ 30% Hepcidin 5 - 50 nmol/L 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. Iron treatment from 1 week before study medication administration until 1 week after study medication administration. Previous enrollment in this study Current or previous (within 60 days before study medication administration) treatment with another investigational drug and/or medical device or participation in another clinical study. Pregnancy or breast-feeding women of child bearing age. Known allergy to any component of the PRS-080#022-DP formulation Positive for hepatitis B surface antigen, anti-hepatitis C virus antibody, or human immunodeficiency virus Planned surgery during the study period Unwilling or unable to comply with the protocol, in the judgment of the investigator Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, apoplexy or coronary artery bypass grafting <3 months prior screening. Congestive heart failure: New York Heart Association Class III or IV.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRS-080#022-DP<br>Hepcidin antagonist, single administration, ascending doses | Biological: PRS-080#022-DP<br>* Hepcidin antagonism to mobilize iron and to treat anemia<br>* Other names: PRS-080;|
| Placebo Comparator: PRS-080-Placebo#001<br>Comparator treatment, single administration | Biological: PRS-080-Placebo#001<br>* Placebo comparator<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events | Composite measure including signs and symptoms, changes from baseline heart rate and blood pressure, ECG, body temperature, respiratory rate clinical chemistry and hematology | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of PRS-080#022 | Area under the plasma concentration versus time curve (AUC) of PRS-080 in plasma | 28 days | 
| Effects of PRS-080#022 on serum iron | Changes in total serum iron concentration compared to baseline | 28 days | 
| Effects of PRS-080#022 on ferritin | Changes in serum ferritin concentration compared to baseline | 28 days | 
| Effects of PRS-080#022 on transferrin saturation | Changes in serum transferrin saturation compared to baseline | 28 days | 
| Effect of PRS-080#022 on hepcidin concentrations in plasma | Changes in hepcidin concentration compared to baseline | 28 days | 
| Number of patients developing anti-drug antibodies | Number of patients with antibodies against PRS-080#022 at day 28 compared to baseline. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepcidin, hemoglobin, iron, anemia of chronic disease