Safety and Tolerability Study of APN01 (Recombinant Human Angiotensin Converting Enzyme 2)
Primary Purpose
Pulmonary Diseases, Cardiovascular Diseases, Kidney Diseases
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
APN01
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Diseases focused on measuring RAS, ACE2, Cardiovascular, Pulmonary, Angiotensin II, Angiotensin 1-7
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.
Sites / Locations
- University Hospital Basel
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
APN01
Placebo
Arm Description
Healthy volunteers will receive APN01
Physiological saline administrated i.v.
Outcomes
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00886353
Brief Title
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
2. Study Status
Record Verification Date
December 2009
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Apeiron Biologics
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Diseases, Cardiovascular Diseases, Kidney Diseases, Cancer Diseases
Keywords
RAS, ACE2, Cardiovascular, Pulmonary, Angiotensin II, Angiotensin 1-7
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
APN01
Arm Type
Active Comparator
Arm Description
Healthy volunteers will receive APN01
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Physiological saline administrated i.v.
Intervention Type
Biological
Intervention Name(s)
APN01
Intervention Description
APN01, a physiological formulation of recombinant human Angiotensin Converting Enzyme 2 administrated i.v.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Physiological saline administrated i.v.
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan Kraehenbuehl, Prof. Dr.
Organizational Affiliation
University Hospital, Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
23681967
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.
Results Reference
derived
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Safety and Tolerability Study of APN01 (Recombinant Human Angiotensin Converting Enzyme 2)
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