99mTc-rhAnnexin V-128: a First In Man Study in Healthy Volunteers

Study Overview
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Brief Summary
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The objectives of this study are: To determine the safety and tolerability of a single dose of 99mTc-rhAnnexin V-128 administered as an intravenous bolus over 10-20 seconds. To determine the biodistribution, pharmacokinetics and radiation dosimetry of 99mTc-rhAnnexin V-128 in normal healthy adult volunteers.

Official Title
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A Phase I Study of Safety, Tolerance, Pharmacokinetics and Nuclear Medicine Imaging of 99mTc-rhAnnexin V-128 Administered Intravenously in Healthy Adult Volunteers

Conditions
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Healthy Adult Volunteers

Intervention / Treatment
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* Drug: Kit for the Preparation of 99mTc-rhAnnexin V-128


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 65 years No significant medical history Normal physical examination No clinically significant abnormalities in baseline laboratory values No clinically significant abnormalities on 12 lead electrocardiogram Female subjects must be post-menopausal, surgically sterilized or have negative urine beta human chorionic gonadotropin pregnancy test at initial screening and pre-injection on dosing day Written informed consent signed Exclusion Criteria: Pregnancy or lactation Know hypersensitivity to the investigational drug or any of its components Current enrolment in another investigational study Unwillingness to provide or continue informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99mTc-rhAnnexin V-128<br> | Drug: Kit for the Preparation of 99mTc-rhAnnexin V-128<br>* Kit for the Preparation of Tc-99m Recombinant Human Annexin V-128 for Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Type and incidence of AEs, as well as severity and relatedness to the study medication will be tabulated. Special attention will be given to those subjects who prematurely discontinue the study or the study medication due to an AE, or who experience a severe AE or an SAE. | Whole study period | 
| Laboratory assessments | Laboratory data (Hematology, coagulation, biochemistry, and urinalysis) will be analysed with respect to the normal ranges of values provided by the local laboratory and with respect to pre-defined levels of change in these values. Abnormal laboratory test results will be tabulated. | baseline and 24 hrs, 72 hrs and 30 days after injection | 
| Electrocardiography | ECG parameters will include heart rate (HR), RR interval, PR interval, QRS width and QT interval. ECG results will be evaluated by means of descriptive statistics and frequency tabulations. | screening and immediatly, 24hrs, 72 hrs, 7 days and 30 days after injection | 
| Vital signs | Descriptive statistics of the vital signs (pulse rate and blood pressure) observed values as well as for the changes from baseline value will be created. Frequency tabulations with values within, below or above the normal ranges will be made. | At each study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rhAnnexin V-128 serum concentration | In addition to dosimetry, pharmacokinetic will be assessed based on rhAnnexin V-128 serum concentration | 0, 5, 10, 15, 30, 60, 90, minutes and 3 h, 6h and 24 h post-injection | 
| Whole-body SPECT imaging | The quantitative in vivo biodistribution (whole body dosimetry) of the 99mTc-rhAnnexin V-128 will be determined through whole-body SPECT imaging. | 30min, 90min, 3hrs, 6hrs and 24 hours post-injection | 
| Blood sample counting | Radioactivity of the whole blood and serum samples will be counted in a gamma counter to assess blood dosimetry and pharmacokinetic. | baseline and 0, 5,10, 15, 30, 60, 90 min, 3 h, 6 h and 24 hours post-injection | 
| Amount of 99mTc excreted in urine |  | One sample at baseline and urine collection within 24 hours post-injection | 
| Amount of 99mTc excreted in faeces |  | Baseline and within 24h post injection | 
| Anti-rhAnnexin V-128 IgG and IgM antibodies |  | Baseline and 14 and 30 days post-injection |