EBV Infections, Kidney Transplant
Conditions
Brief summary
This clinical study will evaluate the safety and tolerability of an IDO-1 inhibitor in patients receiving a kidney transplant. The study includes individuals who have not previously been infected with Epstein-Barr virus (EBV) and who receive a kidney from a donor with prior EBV infection. Participants will receive the IDO-1 inhibitor or placebo in addition to standard medical care and will be monitored for side effects and other safety-related outcomes throughout the study.
Detailed description
This clinical study is being conducted to evaluate the safety and tolerability of an IDO-1 inhibitor in patients receiving a kidney transplant. The study population includes individuals who are Epstein-Barr virus (EBV) seronegative and receive a kidney from an EBV-seropositive donor, a group at increased risk for EBV-related complications following transplantation. Kidney transplantation requires substantial immunosuppression to maintain graft function. While necessary, this immunosuppression increases susceptibility to infections, including EBV, which may lead to serious clinical consequences in immunocompromised individuals. In this study, participants will receive the IDO-1 inhibitor or placebo in addition to standard-of-care immunosuppressive therapy. Study treatment will be initiated prior to kidney transplantation or on the day of transplantation, depending on donor availability, and will be administered for a defined treatment period, followed by a safety follow-up phase. The primary objective of the study is to assess the safety and tolerability of the IDO-1 inhibitor in kidney transplant recipients, including the incidence of adverse events and clinically relevant laboratory abnormalities.
Interventions
DRUGindoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor
Study treatment will be initiated one day prior to kidney transplantation or, for recipients of cadaveric donor organs, on the day of transplantation, and will be administered at a dose of 200 mg once daily for a total duration of 28 days, followed by a safety follow-up phase.
DRUGplacebo
A matching placebo will be administered once daily, initiated one day prior to kidney transplantation or, for recipients of cadaveric donor organs, on the day of transplantation, for a total duration of 28 days, followed by a safety follow-up phase.
Sponsors
University Hospital, Basel, Switzerland
Hornet Therapeutics.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
A randomised, controlled, double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide informed consent 2. Male or female aged ≥18 years 3. EBV seronegative at the time of renal transplant 4. If women of child-bearing potential (WOCBP), participants must have a negative serum pregnancy test at screening and inclusion, and must be willing to use a highly effective method of birth control for the duration of the study. Acceptable methods of contraception: 1. Hormonal contraception associated with inhibition of ovulation 2. Intrauterine device (IUD) 3. Intrauterine hormone-releasing system (IUS) 4. Bilateral tubal occlusion 5. Vasectomised partner 6. Condom with spermicide 7. Sexual abstinence, in line with the preferred and usual lifestyle of the participant. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 5. If male, participants must be prepared to use reliable barrier method contraception and a second method such as spermicide for the duration of the study unless surgically sterile.
Exclusion criteria
1. EBV seropositivity at the time of transplant 2. Participants with any form of cancer within the last 12 months, or patients continuing to receive chemo or immunotherapy within the last 12 months. 3. Participants with a history of PTLD 4. Other active systemic infections requiring treatment prior to and at the time of baseline. Prophylactic agents are permitted. 5. CYP3A4 and CYP2C28 Inhibitors and Inducers (List may be found in Appendix 1) 6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3 x ULN 7. Any condition for which, in the opinion of the investigator, the treatment or participation in the study may pose a health risk to the participant 8. Planned or active participation in any other study with an investigational medicinal product (IMP). 9. Have taken an IMP within the last 3 months. 10. Unwilling or unable to provide fully informed consent. 11. Unwilling or unable to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | up to 12 weeks post-treatment | — |
| Incidence of serious adverse events | up to 12 weeks post-treatment | — |
| Number of participants experiencing adverse events | up to 12 weeks post-treatment | — |
| Number of participants experiencing clinically significant changes in safety assessments | up to 12 weeks post-treatment | Safety assessments include vital signs (pulse rate, blood pressure, and body temperature), 12-lead electrocardiogram (ECG), and laboratory evaluations (haematology and serum/plasma biochemistry), assessed up to and including 12 weeks post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in EBV viral load | up to 12 weeks post-treatment | Assessment EBV viral load in the event of a primary EBV infection |
| Changes in EBV viral dynamics | up to 12 weeks post-treatment | Assessment of EBV viral dynamics in the event of a primary EBV infection |
| Exploratory metabolomic analysis | up to 12 weeks post-treatment | including parameters related to the kynurenine pathway |
| Exploratory analysis peripheral blood mononuclear cells (PBMCs) | up to 12 weeks post-treatment | — |
Countries
Switzerland
Contacts
CONTACTPietro Ernesto Cippà, Prof.
PRINCIPAL_INVESTIGATORMatthias Diebold
University Hospital, Basel, Switzerland
Outcome results
None listed