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

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

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.

Study Overview

• Status: Unknown
• Conditions: Anemia of Chronic Kidney Disease
• Intervention / Treatment: Biological: PRS-080#022-DP; Biological: PRS-080-Placebo#001

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • St. Joseph Krankenhaus
  • Munich, Germany
    • Technical University, Medical Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pieris Pharmaceuticals GmbH
• Collaborators: FGK Clinical Research GmbH
• Investigators: Principal Investigator: Lutz Renders, Prof. MD, Technical University, Munich

Publications and helpful links

Helpful Links

• Pieris Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2016
• Primary Completion (Actual): February 6, 2017
• Study Completion (Anticipated): December 31, 2017

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): October 20, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: hemoglobin; Hepcidin; iron; anemia of chronic disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: PCS_02_15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No