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

NCT ID: NCT03325621

Last Updated: 2019-10-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-30
• Study Completion Date: 2019-06-30

Brief Summary

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.

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.

Conditions

Anemia of Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PRS-080#022-DP

Experimental: PRS-080#022-DP Hepcidin antagonist, repeated administrations, ascending doses

Group Type: ACTIVE_COMPARATOR

PRS-080#022-DP

Intervention Type: BIOLOGICAL

Biological/Vaccine: PRS-080#022-DP Hepcidin antagonism to mobilize iron and to treat anemia

PRS-080-Placebo#001

Experimental: PRS-080-Placebo#001 Comparator treatment, repeated administrations

Group Type: PLACEBO_COMPARATOR

PRS-080-Placebo#001

Intervention Type: BIOLOGICAL

Placebo Comparator

Interventions

PRS-080#022-DP

Biological/Vaccine: PRS-080#022-DP Hepcidin antagonism to mobilize iron and to treat anemia

Intervention Type: BIOLOGICAL

PRS-080-Placebo#001

Placebo Comparator

Intervention Type: BIOLOGICAL

Other Intervention Names

PRS-080; Placebo

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FGK Clinical Research GmbH

INDUSTRY

Sponsor Role: collaborator

Pieris Pharmaceuticals GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lutz Renders, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Technical University, Munich

Ondřej Viklický, Prof.MD

Role: PRINCIPAL_INVESTIGATOR

Institute of Clinical and Experimental Medicine Nephrology Clinic Prague

Locations

University Hospital Brno

Brno, , Czechia

HDS - Klaudian's Hospital

Mladá Boleslav, , Czechia

Institute of Clinical and Experimental Medicine (ICEM)

Prague, , Czechia

VFN Strahov

Prague, , Czechia

MZV DaVita

Düsseldorf, , Germany

Technical University Munich

Munich, , Germany

Countries

Czechia; Germany

Other Identifiers

PCS_03_16

Identifier Type: -

Identifier Source: org_study_id