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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pulmonary Diseases, Cardiovascular Diseases, Kidney Diseases, Cancer Diseases

Intervention / Treatment
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* Biological: APN01
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACE2, Cardiovascular, Pulmonary, Angiotensin II, Angiotensin 1-7, RAS