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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PRS-080#022-DP
* Drug: PRS-080-Placebo#001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Subjects should have a body mass index of 18-30 kg/m2 and should weigh 60-90 kg 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. Willing to comply with the requirements of the study protocol and signing the informed consent sheet. Exclusion Criteria: Any uncontrolled or active major systemic disease History or presence of malignancy Definite or suspected history of drug allergy Active acute or chronic infection, including, but not limited to: upper airway infection, urinary tract infection, and skin infection Use of any investigational drug within 30 days, or 5 half-lives, whichever is longer, prior to the planned first drug administration. 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 Smoking greater than 20 cigarettes per week History of alcohol or substance abuse within the past 6 months prior to the planned first drug administration History of increased bleeding risk Clinically relevant abnormalities found in physical examination, vital signs measurements, laboratory safety tests or ECG Blood donation within the last 60 days prior to the planned first drug administration Positive results on hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV1/2) antibodies screening Iron overload or disturbance in utilization of iron (defined as ferritin > 300.0 ng/mL and < 10.0 ng/mL) i.v. iron treatment or blood transfusion within last 90 days prior to the planned first drug administration or during trial ESA (e.g. Erythropoietin) treatment within the last year Surgery or trauma with significant blood loss within 2 months before the planned first drug administration Not able to abstain from consumption of food or beverages known to influence dietary iron absorption

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRS-080#022-DP<br>hepcidin antagonist, single administration, ascending doses | Drug: PRS-080#022-DP<br>* hepcidin antagonist<br>* Other names: PRS-080;|
| Placebo Comparator: PRS-080-Placebo#001<br>Comparotor treatment, single administration | Drug: PRS-080-Placebo#001<br>* Placebo treatment<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Composite measure including signs and symptoms, local reactions, changes from baseline heart rate and blood pressure, ECG, body temperature, respiratory rate, clinical chemistry and hematology, coagulation and urinalysis over a 28 day period | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of PRS-080#22-DP following administration of single doses | Area under the plasma concentration versus time curve (AUC) of PRS-080#22-DP in blood | 14 time points up to 11 days | 
| Assessment of anti-drug antibodies in blood following single administration | Analysis of antibodies against PRS-080#22-DP at day 28 compared to baseline | up to 28 days | 
| Effect of PRS-080#22-DP on hepcidin concentrations in blood | Changes in hepcidin concentration compared to baseline | 15 time points up to 28 days | 
| Effect of PRS-080#22-DP on total iron | Changes in total iron concentration in blood compared to baseline | up to 28 days | 
| Effect of PRS-080#22-DP on transferrin saturation | Changes in transferrin saturation in blood compared to baseline | up to 28 days | 
| Effect of PRS-080#22-DP on ferritin | Changes to ferritin concentration in blood compared to baseline | up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Subjects