A Study of the Pharmacokinetics, Biodistribution and Dosimetry of Granzyme-B Targeted [Cu-64]-Labeled PET Radiotracers in Adult Healthy Volunteers
Purpose
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.
Condition
- Healthy Volunteer
Eligibility
- Eligible Ages
- Between 18 Years and 60 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Adult male or female participants 18-60 years of age judged to be in good health by the Investigator 2. No clinically significant laboratory abnormalities; all tests of liver and kidney function within normal limits 3. Capable of giving signed informed consent, which includes compliance with requirements and restrictions listed in the ICF and this protocol 4. 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) 2. Inadequate venous access (at least two distinct access sites allowing for separate test agent administration and PK blood sampling are required) 3. Inability or unwillingness to undergo serial PET/CT imaging 4. Active infection or malignancy 5. Known or suspected inflammatory, autoimmune or fibrotic disease 6. Major surgery or other intensive medical treatment in the 3 months prior to planned study injection, as assessed by the investigator 7. Received a radioisotope within 7 physical half-lives of that radioisotope prior to planned study injection 8. Known allergy/hypersensitivity to PET/CT tracers or compounds similar to GzmB-Targeted Compounds 9. Concurrent participation in a clinical trial of investigational product(s) 10. 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 11. 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
Study Design
- Phase
- Early Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Diagnostic
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental [Cu-64]RTX-4001 |
Arm Description: Single IV administration of [Cu-64]RTX-4001, a Granzyme-B-targeted PET radiotracer, in healthy adult volunteers. |
|
|
Experimental [Cu-64]RTX-4002 |
Arm Description: Single IV administration of [Cu-64]RTX-4002, a Granzyme-B-targeted PET radiotracer, in healthy adult volunteers. |
|
Recruiting Locations
New Haven, Connecticut 06510
More Details
- Status
- Recruiting
- Sponsor
- Ratio Therapeutics, Inc.
Detailed Description
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.