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

Sponsor

Pieris Pharmaceuticals GmbH (Industry)

Overall Status

Unknown status

CT.gov ID

NCT02754167

Collaborator

FGK Clinical Research GmbH (Industry)

Enrollment

Locations

Arms

18.8

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia of Chronic Kidney Disease	Biological: PRS-080#022-DP Biological: PRS-080-Placebo#001	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 6, 2016

Actual Primary Completion Date :

Feb 6, 2017

Anticipated Study Completion Date :

Dec 31, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.