Safety and Tolerability Study of APN01 (Recombinant Human Angiotensin Converting Enzyme 2) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pulmonary Diseases Cardiovascular Diseases Kidney Diseases Cancer Diseases	Biological: APN01 Other: Placebo	Phase 1


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Double-blind, Placebo-controlled Dose-escalation Phase I Study With Recombinant Human Soluble Angiotensin Converting Enzyme 2 (rhACE2) APN01 in Healthy Volunteers

Further study details as provided by Apeiron Biologics:

Primary Outcome Measures:

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 [ Time Frame: 31 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: 31 days ] [ Designated as safety issue: No ]


Estimated Enrollment:	22
Study Start Date:	April 2009
Study Completion Date:	December 2009
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886353

Locations


Switzerland
University Hospital Basel
Basel, Switzerland, 4031

Sponsors and Collaborators

Apeiron Biologics

Investigators


Principal Investigator:	Stephan Kraehenbuehl, Prof. Dr.	University Hospital, Basel, Switzerland

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Haschke M, Schuster M, Poglitsch M, Loibner H, Salzberg M, Bruggisser M, Penninger J, Krähenbühl 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.


Responsible Party:	Prof. Dr. Krähenbühl, Chefarzt klinische Pharmakologie & Toxikologie, Universitätsspital 4031 Basel
ClinicalTrials.gov Identifier:	NCT00886353 History of Changes
Other Study ID Numbers:	APN01-1-01
Study First Received:	April 20, 2009
Last Updated:	December 30, 2009
Health Authority:	Switzerland: Swissmedic

Keywords provided by Apeiron Biologics:


RAS ACE2 Cardiovascular	Pulmonary Angiotensin II Angiotensin 1-7

Additional relevant MeSH terms:


Lung Diseases Cardiovascular Diseases Kidney Diseases Respiratory Tract Diseases Urologic Diseases

ClinicalTrials.gov processed this record on September 23, 2016