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

Anemia of Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03325621
• Other study ID #: PCS_03_16
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 30, 2017
• Est. completion date: June 30, 2019

Study information

• Verified date: November 2018
• Source: Pieris Pharmaceuticals GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: June 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anemia of Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Biological:
• PRS-080#022-DP
Biological/Vaccine: PRS-080#022-DP Hepcidin antagonism to mobilize iron and to treat anemia
• PRS-080-Placebo#001
Placebo Comparator

Locations

Country	Name	City	State
Czechia	University Hospital Brno	Brno
Czechia	HDS - Klaudian's Hospital	Mladá Boleslav
Czechia	Institute of Clinical and Experimental Medicine (ICEM)	Prague
Czechia	VFN Strahov	Prague
Germany	MZV DaVita	Düsseldorf
Germany	Technical University Munich	Munich

Sponsors (2)

Lead Sponsor	Collaborator
Pieris Pharmaceuticals GmbH	FGK Clinical Research GmbH

Countries where clinical trial is conducted

Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cmax	Measuring the maximum concentration of PRS-080#022 in the blood	112 days
Secondary	Effects of PRS-080#022 on serum iron	Changes in total serum iron concentration compared to baseline	56 days
Secondary	Effects of PRS-080#022 on ferritin	Changes in serum ferritin concentration compared to baseline	56 days
Secondary	Effects of PRS-080#022 on transferrin saturation	Changes in serum transferrin saturation compared to baseline	56 days
Secondary	Effect of PRS-080#022 on hepcidin concentrations in plasma	Changes in hepcidin concentration compared to baseline	56 days
Secondary	Number of patients developing anti-drug antibodies	Number of patients with antibodies against PRS-080#022 at day 28 compared to baseline	112 days
Secondary	Effects on red blood cell Hb concentration	Changes in Hb concentration compared to baseline	56 days
Secondary	ctrough	Measuring the concentration of PRS-080#022 before the drug application	112 days
Secondary	tmax	Evaluation of the time for PRS-080#022 to reach maximum concentration	112 days
Secondary	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

External Links

•   Pieris Pharmaceuticals