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

• ClinicalTrials.gov Identifier: NCT00886353
• Recruitment Status: Completed
• First Posted: April 22, 2009
• Last Update Posted: December 31, 2009
• Sponsor: Apeiron Biologics
• Information provided by: Apeiron Biologics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Diseases; Cardiovascular Diseases; Kidney Diseases; Cancer Diseases	Biological: APN01; Other: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: April 2009
• Actual Primary Completion Date: November 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: APN01-1-01
• First Posted: April 22, 2009
• Last Update Posted: December 31, 2009
• Last Verified: December 2009

Keywords provided by Apeiron Biologics:

RAS; ACE2; Cardiovascular; Pulmonary; Angiotensin II; Angiotensin 1-7

Additional relevant MeSH terms:

Kidney Diseases; Cardiovascular Diseases; Urologic Diseases