First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PRS-080

A First-in-Human, Randomized, Dose-Escalation, Double-Blind, Placebo-Controlled Single Ascending Dose Study to Establish Safety, Lack of Immunogenicity, Tolerability, Pharmacokinetic Parameters, Target Engagement and Pharmacodynamic Effects

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 treatment of anemia of chronic disease. This phase I First-in-Human study shall investigate safety and pharmacokinetics in healthy human volunteers.

First-in-Human (FIH), randomized, dose-escalation, double-blind, placebo-controlled single dose in healthy volunteers.

The single rising dose study will enroll 8 subjects per cohort (6 verum, 2 placebo), up to a maximum tolerated dose, defined by stopping rules. 6 dose levels are anticipated. Study drug will be administered as i.v. infusion on Day 1. The decision to escalate the dose by the dose escalation committee (DEC) will be based on an interim analysis of clinical safety and safety laboratory data.

Inclusion Criteria:

1. Healthy Caucasian males: based on a screening examination including medical history, physical examination, 12-lead ECG, vital signs and clinical laboratory profiles, age 18-50 years
2. Subjects should have a body mass index of 18-30 kg/m2 and should weigh 60-90 kg
3. Subjects must be using two acceptable methods for contraception (e.g. spermicide and condom) during the study and refrain from fathering a child in the 3 months following the last dosing.
4. Willing to comply with the requirements of the study protocol and signing the informed consent sheet.

Exclusion Criteria:

1. Any uncontrolled or active major systemic disease
2. History or presence of malignancy
3. Definite or suspected history of drug allergy
4. Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, and skin infection
5. Use of any investigational drug within 30 days, or 5 half-lives, whichever is longer, prior to the planned first drug administration.
6. Use of prescription medication within 14 days prior to the planned first drug administration and throughout the study (with the exception of medications given to treat an adverse event and use of non-prescription or over-the-counter medications within 7 days prior to the planned first drug administration and throughout the study (including vitamins, herbal supplements, or remedies
7. Smoking greater than 20 cigarettes per week
8. History of alcohol or substance abuse within the past 6 months prior to the planned first drug administration
9. History of increased bleeding risk
10. Clinically relevant abnormalities found in physical examination, vital signs measurements, laboratory safety tests or ECG
11. Blood donation within the last 60 days prior to the planned first drug administration
12. Positive results on hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV1/2) antibodies screening
13. Iron overload or disturbance in utilization of iron (defined as ferritin > 300.0 ng/mL and < 10.0 ng/mL)
14. i.v. iron treatment or blood transfusion within last 90 days prior to the planned first drug administration or during trial
15. ESA (e.g. Erythropoietin) treatment within the last year
16. Surgery or trauma with significant blood loss within 2 months before the planned first drug administration
17. Not able to abstain from consumption of food or beverages known to influence dietary iron absorption