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

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00886353
• Other study ID #: APN01-1-01
• Status: Completed
• Phase: Phase 1
• First received: April 20, 2009
• Last updated: December 30, 2009
• Start date: April 2009
• Est. completion date: December 2009

Study information

• Verified date: December 2009
• Source: Apeiron Biologics
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer Diseases
• Cardiovascular Diseases
• Kidney Diseases
• Pulmonary Diseases

Intervention

Biological:
• APN01
APN01, a physiological formulation of recombinant human Angiotensin Converting Enzyme 2 administrated i.v.

Other:
• Placebo
Physiological saline administrated i.v.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
Apeiron Biologics

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No