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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PRS-080#022-DP; Drug: PRS-080-Placebo#001

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neu-Ulm, Germany
    • Nuvisan GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pieris Pharmaceuticals GmbH
• Collaborators: FGK Clinical Research GmbH; Nuvisan Pharma Services; EUROCALIN Consortium
• Investigators: Study Director: Ulrich Moebius, PhD, Pieris Pharmaceuticals GmbH

Publications and helpful links

Helpful Links

• Pieris AG

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: December 18, 2014
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 16, 2015

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: August 7, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Subjects
• Other Study ID Numbers: PCS_01_12