Cytomegalovirus (CMV) Infection, Kidney Transplant Recipient
Conditions
Keywords
Cytomegalovirus, Kidney Transplantation, Ex-vivo organ perfusion
Brief summary
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).
Detailed description
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.
Interventions
DRUGSYN002
SYN002, a fusion protein targeting US28, a human cytomegalovirus (CMV) - specific virally encoded receptor expressed on both latent and lytic CMV-infected cells.
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
Interventional Phase 1 Single Group Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft function | 4 weeks post-transplant | Proportion of patients with a functioning graft at 4 weeks post-transplant defined as no longer needing dialysis at 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delayed graft function | 4 weeks post-transplant | a. Proportion of patients with delayed graft function with requirement for dialysis post-transplant |
| CMV DNAemia 3 months | 3 months post-transplant | Proportion of patients that develop CMV DNAemia with plasma viral load \> 1000 IU/ml at 3 months post-transplant |
| Length of hospital stay | 6 months post-transplant | Median days of hospital stay |
| Graft survival 3 months | 3 months post-transplant | Proportion of patients with a functioning graft |
| Graft survival 6 months | 6 months | Proportion of patients with a functioning graft |
| CMV DNAemia 6 months | 6 months post-transplant | Proportion of patients that develop CMV DNAemia with plasma viral load \> 1000 IU/ml at 6 months post-transplant |
| CMV disease | 6 months post-transplant | Proportion of patients with CMV disease |
Countries
Canada
Contacts
CONTACTAtul Humar, MD, FRCP(C)
Outcome results
None listed