A Study of the Pharmacokinetics, Biodistribution and Dosimetry of Granzyme-B Targeted [Cu-64]-Labeled PET Radiotracers in Adult Healthy Volunteers

Granzyme B (GzmB) is a cytotoxic serine protease released by activated T cells and natural killer cells, and its release acts as a functional marker of immune engagement. GzmB-Targeted [Cu-64]-labeled compounds are being developed as PET/CT tracers to image immune activation and inflammation. This first-in-human Phase 0 study in adult healthy volunteers is designed to characterize the pharmacokinetics, biodistribution, radiation dosimetry, and safety of GzmB-targeted [Cu-64]-labeled compounds.

Up to 6 participants (3 female, 3 male) will receive a single dose of a GzmB-targeted [Cu-64]-labeled compound, followed by serial whole-body PET/CT imaging, blood and urine sampling for pharmacokinetics and excretion, and safety assessments over approximately 24 hours post-dose, with a telephone follow-up at about 7 days. Up to 2 GzmB-Targeted [Cu-64]-labeled compounds may be assessed in the clinical trial (i.e. a maximum of 12 healthy volunteers in total in the study).

Data from this study will support lead candidate selection and inform further clinical development of a [Cu-64]-labeled GzmB-targeted imaging agent.

Inclusion criteria

• 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.

Exclusion criteria

• 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
• Known or suspected inflammatory, autoimmune or fibrotic disease
• Major surgery or other intensive medical treatment in the 3 months prior to planned study injection, as assessed by the investigator
• Received a radioisotope within 7 physical half-lives of that radioisotope prior to planned study injection
• Known allergy/hypersensitivity to PET/CT tracers or compounds similar to GzmB-Targeted Compounds
• Concurrent participation in a clinical trial of investigational product(s)
• Participation in other research protocols or clinical care where there was radiation exposure such that the exposure from the last year, in addition to the radiation exposure expected from participation in this clinical study, exceeds the effective dose of 50 mSv, which would be above the acceptable annual limit established by US federal guidelines
• Significant intercurrent illness or psychiatric illness/social situation that could place the participant at undue risk during study participation, significantly alter study outcomes, or affect participant compliance with study requirements for dosing and evaluation, as determined by the investigator