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.

Study Overview

• Status: Completed
• 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, 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 625 00
    • University Hospital Brno
  • Mladá Boleslav, Czechia, 293 50
    • HDS - Klaudian's Hospital
  • Prague, Czechia, 140 21
    • Institute of Clinical and Experimental Medicine (ICEM)
  • Prague, Czechia, 169 00
    • VFN Strahov
• Germany
  • Düsseldorf, Germany, 40210
    • MZV DaVita
  • Munich, Germany, 81675
    • Technical University Munich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

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
Active Comparator: PRS-080#022-DP; Experimental: PRS-080#022-DP Hepcidin antagonist, repeated administrations, ascending doses	Biological: PRS-080#022-DP; Biological/Vaccine: PRS-080#022-DP Hepcidin antagonism to mobilize iron and to treat anemia; Other Names: PRS-080
Placebo Comparator: PRS-080-Placebo#001; Experimental: PRS-080-Placebo#001 Comparator treatment, repeated administrations	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	112 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Measuring the maximum concentration of PRS-080#022 in the blood	112 days
Effects of PRS-080#022 on serum iron	Changes in total serum iron concentration compared to baseline	56 days
Effects of PRS-080#022 on ferritin	Changes in serum ferritin concentration compared to baseline	56 days
Effects of PRS-080#022 on transferrin saturation	Changes in serum transferrin saturation compared to baseline	56 days
Effect of PRS-080#022 on hepcidin concentrations in plasma	Changes in hepcidin concentration compared to baseline	56 days
Number of patients developing anti-drug antibodies	Number of patients with antibodies against PRS-080#022 at day 28 compared to baseline	112 days
Effects on red blood cell Hb concentration	Changes in Hb concentration compared to baseline	56 days
ctrough	Measuring the concentration of PRS-080#022 before the drug application	112 days
tmax	Evaluation of the time for PRS-080#022 to reach maximum concentration	112 days
Elimination of PRS-080#022	Evaluation of Terminal rate constant and terminal half-life (t½ ) after the very last administration of PRS-080 in plasma	112 days

Collaborators and Investigators

• Sponsor: Pieris Pharmaceuticals GmbH
• Collaborators: FGK Clinical Research GmbH
• Investigators: Principal Investigator: Lutz Renders, Prof. MD, Technical University, Munich; Principal Investigator: Ondřej Viklický, Prof.MD, Institute of Clinical and Experimental Medicine Nephrology Clinic Prague

Publications and helpful links

Helpful Links

• Pieris Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2017
• Primary Completion (Actual): March 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: October 19, 2017
• First Submitted That Met QC Criteria: October 27, 2017
• First Posted (Actual): October 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Iron; Hepcidin; Hemoglobin; Anemia of chronic disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: PCS_03_16

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No