Safety and Tolerability Study of APN01 (Recombinant Human Angiotensin Converting Enzyme 2)

Double-blind, Placebo-controlled Dose-escalation Phase I Study With Recombinant Human Soluble Angiotensin Converting Enzyme 2 (rhACE2) APN01 in Healthy Volunteers

The purpose of this study is to define the dose for a Phase II study and to investigate safety and tolerability of intravenous administration of recombinant soluble human Angiotensin Converting Enzyme 2 in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Kidney Diseases; Pulmonary Diseases; Cancer Diseases
• Intervention / Treatment: Biological: APN01; Other: Placebo

Detailed Description

APN01-1-01 is a placebo controlled double blinded Phase I study composed of a single dose, dose escalation part followed by a multiple dosage part. The first four cohorts (four individuals each) will receive 100, 200, 400 and 800 µg/kg APN01 i.v. or placebo. Cohorts 5 and 6 (three individuals each) will receive three and six i.v. APN01 administrations daily, respectively. Planned dosage of the multiple dose part will be 400 µg/kg.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female
• Age ≥18 years
• Use of acceptable form of birth control
• Willing to comply with study protocol
• No significant background illness
• Signed informed consent form

Exclusion Criteria:

• Significant hematological, renal, hepatic, metabolic, psychiatric or pulmonary diseases.
• Heart disease or elevated blood pressure.
• Any other significant disease that could interfere with the subject's ability to complete the protocol
• History of alcohol or drug abuse
• Abnormal urinalysis
• Pregnant or lactating female subjects
• Use of anticoagulants or antihypertensive drugs, particularly drugs interfering with the renin-angiotensin-aldosterone system, Obesity or anorexia (BMI <18 or >30)
• History of malignancy, except basal cell carcinoma of the skin, Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or positive serology testing in the study screening procedures (except indicating immunization)
• Participation in a clinical trial within the last 30 days

• Any of the following laboratory abnormalities:

  • WBC 15% outside of normal limits
  • Hemoglobin 15% outside of normal limits
  • Platelets 15% outside of normal limits
  • Aspartate transferase (AST) or alanine transferase (ALT) above 15% outside of normal limits
  • Alkaline phosphatase above 15% outside of normal limits
  • Urea above 15% outside of normal limits
  • Creatinine above 15% outside of normal limits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: APN01; Healthy volunteers will receive APN01	Biological: APN01; APN01, a physiological formulation of recombinant human Angiotensin Converting Enzyme 2 administrated i.v.
Placebo Comparator: Placebo; Physiological saline administrated i.v.	Other: Placebo; Physiological saline administrated i.v.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability profile of APN01 when administered as a single dose / multiple dose i.v. in healthy volunteers. Measures: Blood chemistry, Hematology, Urinalysis, Adverse events, Vital signs including blood pressure, pulse, respiratory rate, ECG	31 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
To obtain pharmacokinetic and pharmacodynamic data for APN01 and to investigate potential immunogenicity of APN01. Measures: Systemic rhACE2 concentration and activity, potential humoral immune response, Angiotensin II and Angiotensin 1-7 plasma levels.	31 days

Collaborators and Investigators

• Sponsor: Apeiron Biologics
• Investigators: Principal Investigator: Stephan Kraehenbuehl, Prof. Dr., University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Haschke M, Schuster M, Poglitsch M, Loibner H, Salzberg M, Bruggisser M, Penninger J, Krahenbuhl S. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clin Pharmacokinet. 2013 Sep;52(9):783-92. doi: 10.1007/s40262-013-0072-7.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: April 21, 2009
• First Posted (Estimate): April 22, 2009

Study Record Updates

• Last Update Posted (Estimate): December 31, 2009
• Last Update Submitted That Met QC Criteria: December 30, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Cardiovascular; Pulmonary; RAS; Angiotensin II; ACE2; Angiotensin 1-7
• Additional Relevant MeSH Terms: Urologic Diseases; Cardiovascular Diseases; Kidney Diseases
• Other Study ID Numbers: APN01-1-01