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

Phase 1

• Conditions: Anemia of Chronic Kidney Disease
• Interventions: Biological: PRS-080#022-DP; Biological: PRS-080-Placebo#001

• Registration Number: NCT02754167
• Lead Sponsor: Pieris Pharmaceuticals GmbH

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-04-14
• Study First Submitted QC: 2016-04-27
• Study First Posted: 2016-04-28
• Study Start: 2016-06-06
• Primary Completion: 2017-02-06
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-19
• Last Update Posted: 2017-10-20
• Study Completion: 2017-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PRS-080#022-DP	PRS-080#022-DP	Hepcidin antagonist, single administration, ascending doses
PRS-080-Placebo#001	PRS-080-Placebo#001	Comparator treatment, single administration

Primary Outcome Measures

Name	Time	Method
Number of patients with adverse events	28 days	Composite measure including signs and symptoms, changes from baseline heart rate and blood pressure, ECG, body temperature, respiratory rate clinical chemistry and hematology

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Technical University, Medical Department; 🇩🇪 Munich, Germany

St. Joseph Krankenhaus; 🇩🇪 Berlin, Germany