This is an exploratory clinical study of copper-64 \[Cu-64\]-labeled granzyme B (GzmB)-targeted compounds for PET/CT imaging. The goal is to determine how GzmB-Targeted \[Cu-64\]-labeled compounds are distributed in the body by assessing PET/CT images and blood samples, and to assess the safety profile after a single intravenous dose.
Up to 6 healthy volunteers (3 female, 3 male) will receive one injection of a GzmB-targeted \[Cu-64\]-labeled compound, then undergo multiple whole-body PET/CT scans, blood and urine tests over about 24 hours, and a follow-up phone call around Day 7. Up to 2 GzmB-Targeted \[Cu-64\]-labeled compounds may be assessed (i.e. maximum of 12 healthy volunteers in total in the study).
Researchers will look at the blood activity of GzmB-Targeted \[Cu-64\]-labeled compound and the organ distribution and movement of the product in the body. They will also evaluate any changes in physical examination assessments, vital signs, ECG, and clinical laboratory measurements from pre-administration to post-administration.
Adult male or female participants 18-60 years of age judged to be in good health by the Investigator
No clinically significant laboratory abnormalities; all tests of liver and kidney function within normal limits
Capable of giving signed informed consent, which includes compliance with requirements and restrictions listed in the ICF and this protocol
Female participants of childbearing potential and male participants who are fertile and have female partners of childbearing potential must agree to use adequate birth control throughout the study to the conclusion of follow-up.
Pregnant or breast-feeding female participants (female participants of childbearing potential must have negative pregnancy tests at Screening and pre-dose Day 0)
Inadequate venous access (at least two distinct access sites allowing for separate test agent administration and PK blood sampling are required)
Inability or unwillingness to undergo serial PET/CT imaging
Active infection or malignancy
Sequential
Granzyme-B targeted [64Cu]-labeled PET radiotracer
DrugSingle intravenous administration of a Granzyme-B targeted \[64Cu\]-labeled positron emission tomography (PET) radiotracer to assess pharmacokinetics, biodistribution, and radiation dosimetry in adult healthy volunteers.
Determine the maximum concentration (Cmax) of radiation (Pharmacokinetics) in the blood after a single dose of the GzmB-Targeted [Cu-64]-labeled compound
Blood samples will be collected Pre-dose, immediately post-dose, 45 minutes, 1 \& 4 hours, \& 24 hours post dose. Radiation (PK) to be measured by gamma counter (KBq/mL).
Determine the time to maximum concentration (Tmax) in the blood after a single dose of the GzmB-Targeted [Cu-64]-labeled compound
Blood samples will be collected Pre-dose, immediately post-dose, 45 minutes, 1 \& 4 hours, \& 24 hours post dose. Time to maximum concentration to be measured in hours (h).
Determine the area under the curve (AUC) in blood after a single injection of the GzmB-Targeted [Cu-64]-labeled compound
Blood samples will be collected Pre-dose, immediately post-dose, 45 minutes, 1 \& 4 hours, \& 24 hours post dose. AUC to be calculated by kilobecquerel x hours/milliliter (KBq x h/mL)
Determine the elimination half-life in the blood post a single injection of the GzmB-Targeted [Cu-64]-labeled compound
Blood samples will be collected Pre-dose, immediately post-dose, 45 minutes, 1 \& 4 hours, \& 24 hours post dose. Elimination to be measured by time to half of the product being excreted from the blood (as measured by gamma counter) in hours (h)
Evaluate the radiation absorbed dose estimates for organs for a single dose of the GzmB-Targeted [Cu-64]-labeled compound
Imaging timepoints will be collected at 20 minutes post dose, 1 \& 4 hours, and 24 hours post dose. PET/CT will be used to assess the whole body effective dose as measured by mGy/MBq.
Evaluate the whole body effective dose estimated for a single dose of the GzmB-Targeted [Cu-64]-labeled compound
Imaging timepoints will be collected at 20 minutes post dose, 1 \& 4 hours, and 24 hours post dose. PET/CT will be used to assess the whole body effective dose as measured by mSv/MBq.
Examine whole-body excretion of a single dose of the GzmB-Targeted [Cu-64] labeled compound
Urine samples will be evaluated for radioactivity levels of GzmB-Targeted \[Cu-64\]-labeled compound. Samples will be measured by gamma counter to evaluate the amount of radiation excreted in each interval Ae(t) (kBq)
Determine the total cumulative excretion over time in the urine (mL/min) for the GzmB-Targeted [Cu-64]-labeled compound
Samples will be taken continuously starting immediately post-dose through 24 hours post injection. Includes all quantified radioactivity as measured by gamma counter in urine up to the least measured timepoint.
Click on the lead sponsor to view all of their trials.
