Safety and Tolerability of IDO-1 Inhibition in the Prevention of EBV-related Pathology in EBV Negative Kidney Transplant Recipients Receiving an Organ From EBV Positive Donors (IDEP)

A Randomised, Controlled, Double-blind Study to Evaluate the Safety and Tolerability of IDO-1 Inhibition in the Prevention of EBV-related Pathology in EBV Negative Kidney Transplant Recipients Receiving an Organ From EBV Positive Donors.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant; EBV Infections
• Intervention / Treatment: Drug: indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pietro Ernesto Cippà, Prof.; Phone Number: +41 61 32 84848; Email: pietro.cippa@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
    • Contact: Matthias Diebold, Dr. med.; Phone Number: +41 61 328 64 22; Email: matthias.diebold@usb.ch
    • Principal Investigator: Pietro Cippà, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; 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.
Experimental: Treatment	Drug: indoleamine 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	up to 12 weeks post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in EBV viral load	Assessment EBV viral load in the event of a primary EBV infection	up to 12 weeks post-treatment
Changes in EBV viral dynamics	Assessment of EBV viral dynamics in the event of a primary EBV infection	up to 12 weeks post-treatment
Exploratory metabolomic analysis	including parameters related to the kynurenine pathway	up to 12 weeks post-treatment
Exploratory analysis peripheral blood mononuclear cells (PBMCs)		up to 12 weeks post-treatment

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Hornet Therapeutics.
• Investigators: Principal Investigator: Matthias Diebold, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Epstein-Barr Virus Infections
• Other Study ID Numbers: 2025-02366; ub24hess

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No