Renal Ex Vivo SYN002 Perfusion to Eliminate CMV Transmission

Официальное название

Renal Ex Vivo SYN002 Perfusion to Eliminate CMV Transmission: A Safety Trial in Kidney Transplant Recipients

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат SYN002
  SYN002, a fusion protein targeting US28, a human cytomegalovirus (CMV) - specific virally encoded receptor expressed on both latent and lytic CMV-infected cells.

Первичные конечные точки

• Graft function [Срок оценки: 4 weeks post-transplant]

Вторичные конечные точки (7)

• Delayed graft function [Срок оценки: 4 weeks post-transplant]
• CMV DNAemia 3 months [Срок оценки: 3 months post-transplant]
• Length of hospital stay [Срок оценки: 6 months post-transplant]
• Graft survival 3 months [Срок оценки: 3 months post-transplant]
• Graft survival 6 months [Срок оценки: 6 months]
• CMV DNAemia 6 months [Срок оценки: 6 months post-transplant]
• CMV disease [Срок оценки: 6 months post-transplant]

Критерии участия

Recipient Inclusion Criteria:

• Age ≥18 years
• Listed for kidney transplantation
• Either CMV seronegative or seropositive
• Willing to provide written informed consent to take part in the trial
• Willing and able to return for follow-up visits as scheduled in the protocol
• Not participating in other interventional trials

Recipient Exclusion Criteria:

• Listed for combined organ transplant (e.g. kidney-pancreas or kidney-liver)
• Re-transplantation
• HIV positive
• Highly sensitized recipient with a PRA >=95
• Planned use of belatacept or alemtuzumab immunosuppression (both non-approved drugs in Canada)
• Unable or unwilling to comply with study procedures

Donor Inclusion Criteria:

• Deceased donor
• CMV seropositive (D+)
• Donor kidney meets criteria for transplantation
• Single renal artery (required anatomy to perform EVOP)

Donor Exclusion Criteria:

• CMV seronegative
• Donor kidney not suitable for transplantation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• University Health Network, Toronto General Hospital, Ajmera Transplant Centre — Toronto

Публикации

• 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.2021.10.01 PMID 34802874
• 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. PMID 40200403

Идентификаторы

NCT: NCT07488481 · 25-5953

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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