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.

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.

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.