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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Volunteers
• Intervention / Treatment: Drug: Kit for the Preparation of 99mTc-rhAnnexin V-128

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, ON K1Y 4W7
      • The University of Ottawa Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 and 65 years
2. No significant medical history
3. Normal physical examination
4. No clinically significant abnormalities in baseline laboratory values
5. No clinically significant abnormalities on 12 lead electrocardiogram
6. 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
7. Written informed consent signed

Exclusion Criteria:

1. Pregnancy or lactation
2. Know hypersensitivity to the investigational drug or any of its components
3. Current enrolment in another investigational study
4. Unwillingness to provide or continue informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Advanced Accelerator Applications
• Collaborators: Atreus Pharmaceuticals Corporation
• Investigators: Principal Investigator: Terrence D. Rudy, MD, FRCPC, The University of Ottawa Heart Institute, The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: July 1, 2014
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 1001 (Registro Nacional Estudios Clinicos (RNEC)); CAAA113A12101 (Other Identifier: Novartis)