Clinical trial NCT00886353: Safety and Tolerability Study of APN01 (Recombinant Human Angiotensin Converting Enzyme 2)
Official title: Double-blind, Placebo-controlled Dose-escalation Phase I Study With Recombinant Human Soluble Angiotensin Converting Enzyme 2 (rhACE2) APN01 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Diseases
Cardiovascular Diseases
Kidney Diseases
Cancer Diseases
Keywords: RAS
ACE2
Cardiovascular
Pulmonary
Angiotensin II
Angiotensin 1-7
Lead sponsor: Apeiron Biologics
Sponsor class: INDUSTRY
First posted: 2009-04-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 31 Days
Secondary outcomes:
measure: 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.
timeFrame: 31 days
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Stephan Kraehenbuehl, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.