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Donor organs often carry latent Cytomegalovirus (CMV) infection that may be transmitted to the recipient. The goal of this clinical trial is to determine the safety of SYN002 treatment during Ex-Vivo Organ Perfusion (EVOP) in clinical kidney transplantation. Donor kidneys will be treated on the EVOP system with SYN002 in order to decrease the burden of latent CMV in the organ and mitigate the transmission of cytomegalovirus (CMV).
Cytomegalovirus (CMV) is the most common viral infection in transplant recipients and has major impacts on patient outcomes. It can cause fever, pneumonia, gastrointestinal disease, and lead to rejection of the kidney. To prevent this, transplant recipients receive prolonged antiviral drugs. This leads to significant drug toxicity and cost, and is often not successful. The risk of CMV is much higher if the donor organ carries latent CMV inside it (approximately 50-70% of donor organs). A much better and safer strategy would therefore be to try to eliminate the latent virus from the donor organ prior to transplantation. Ex Vivo Organ Perfusion (EVOP) is a common method of donor organ preservation and treatment which allows donor organs to be treated for several hours under close to physiological conditions.
The investigators propose a study in which kidneys will be treated prior to transplantation on the EVOP platform in order to decrease latent CMV. SYN002 is a novel compound that binds to cells that are latently infected with CMV and is internalized and kills those specific cells. This pilot study will involve 12 kidney transplant patients, who are receiving a kidney known to have latent CMV. The kidney will be treated with SYN002 on the EVOP system prior to transplantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EVOP with SYN002 | Experimental | Donor kidneys will be treated with SYN002 administered on the EVOP platform. Normothermic perfusion of kidney will be preformed for approximately 4 hours. Prior to transplant, the kidneys will be flushed to remove any residual SYN002 Transplantation and post-operative care will be as per standard of care. The target dose of SYN002 will 850ng/ml; This dose has been shown to be safe and effective in pre-clinical testing. However, we will perform a dose escalation as follows: Cohort 1: 50 ng/ml (n=2); Cohort 2: 150 ng/ml (n=2); Cohort 3: 450 ng/ml (n=2); Cohort 4: 850 ng/ml (n=6). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYN002 | Drug | SYN002, a fusion protein targeting US28, a human cytomegalovirus (CMV) - specific virally encoded receptor expressed on both latent and lytic CMV-infected cells. |
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| Measure | Description | Time Frame |
|---|---|---|
| Graft function | Proportion of patients with a functioning graft at 4 weeks post-transplant defined as no longer needing dialysis at 4 weeks | 4 weeks post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Delayed graft function | a. Proportion of patients with delayed graft function with requirement for dialysis post-transplant | 4 weeks post-transplant |
| CMV DNAemia 3 months | Proportion of patients that develop CMV DNAemia with plasma viral load > 1000 IU/ml at 3 months post-transplant |
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Recipient Inclusion Criteria:
Recipient Exclusion Criteria:
Donor Inclusion Criteria:
Donor Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Atul Humar, MD, FRCP(C) | Contact | 416-340-4241 | atul.humar@uhn.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Health Network, Toronto General Hospital, Ajmera Transplant Centre | Toronto | Ontario | M5G 2N2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34802874 | Background | Ribeiro RVP, Ku T, Wang A, Pires L, Ferreira VH, Michaelsen V, Ali A, Galasso M, Moshkelgosha S, Gazzalle A, Jeppesen MG, Rosenkilde MM, Liu M, Singer LG, Kumar D, Keshavjee S, Sinclair J, Kledal TN, Humar A, Cypel M. Ex vivo treatment of cytomegalovirus in human donor lungs using a novel chemokine-based immunotoxin. J Heart Lung Transplant. 2022 Mar;41(3):287-297. doi: 10.1016/j.healun.2021.10.010. Epub 2021 Oct 25. | |
| 40200403 |
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Only aggregate data will be shared for privacy reasons
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| ID | Term |
|---|---|
| D003586 | Cytomegalovirus Infections |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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Interventional Phase 1 Single Group Assignment
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Open Label
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| 3 months post-transplant |
| Length of hospital stay | Median days of hospital stay | 6 months post-transplant |
| Graft survival 3 months | Proportion of patients with a functioning graft | 3 months post-transplant |
| Graft survival 6 months | Proportion of patients with a functioning graft | 6 months |
| CMV DNAemia 6 months | Proportion of patients that develop CMV DNAemia with plasma viral load > 1000 IU/ml at 6 months post-transplant | 6 months post-transplant |
| CMV disease | Proportion of patients with CMV disease | 6 months post-transplant |
| Background |
| Kotton CN, Kumar D, Manuel O, Chou S, Hayden RT, Danziger-Isakov L, Asberg A, Tedesco-Silva H, Humar A; Transplantation Society International CMV Consensus Group. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025 Jul 1;109(7):1066-1110. doi: 10.1097/TP.0000000000005374. Epub 2025 Apr 9. No abstract available. |