Clinical trial NCT02340572: First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PRS-080
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy Subjects
Lead sponsor: Pieris Pharmaceuticals GmbH
Sponsor class: INDUSTRY
Collaborators: name: Nuvisan Pharma Services
name: FGK Clinical Research GmbH
name: EUROCALIN Consortium
First posted: 2015-01-16
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: up to 28 days
Secondary outcomes:
measure: Pharmacokinetics of PRS-080#22-DP following administration of single doses
timeFrame: 14 time points up to 11 days
measure: Assessment of anti-drug antibodies in blood following single administration
timeFrame: up to 28 days
measure: Effect of PRS-080#22-DP on hepcidin concentrations in blood
timeFrame: 15 time points up to 28 days
measure: Effect of PRS-080#22-DP on total iron
timeFrame: up to 28 days
measure: Effect of PRS-080#22-DP on transferrin saturation
timeFrame: up to 28 days
measure: Effect of PRS-080#22-DP on ferritin
timeFrame: up to 28 days
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Pieris Pharmaceuticals GmbH
name: Ulrich Moebius, PhD
role: STUDY_DIRECTOR
References: