Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (IMPROVE TRIAL)

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Apr 2, 2025

Keywords

ClinConnect Summary

The IMPROVE TRIAL is a study designed to see if a treatment called Berinert can help improve kidney function in patients receiving a transplant from deceased donors, especially those at higher risk. The main goal is to find out if a single injection of Berinert into the donor kidney before transplantation can lead to better kidney function in the first year after the transplant. To understand the effects of Berinert, some participants will receive the treatment, while others will get a placebo—a substance that looks the same but has no active ingredients. Neither you nor the study doctor will know which treatment you receive.

To be eligible for this trial, participants must be adults on dialysis who are waiting for a kidney transplant and are compatible with their donor. Other requirements include being in good health, having no serious infections or certain medical conditions, and being able to agree to use effective birth control if they are of childbearing age. If you decide to participate, you can expect close monitoring and regular check-ups to assess how well your new kidney is functioning. This study aims to provide valuable information that could improve kidney transplant outcomes for many patients in the future.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Participant must be able to understand and provide informed consent
• • 2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
• • 3. Recipients who are ABO compatible with donor allograft
• • 4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
• • 5. Female participants of childbearing potential must have a negative pregnancy test upon study entry
• • 6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant
• • 7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission
• • 8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission
• • 9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
• • 10. Vaccines up to date per Division of Allergy, Immunology, and Transplantation (DAIT) guidance for patients in transplant trials
• • 11. Anticipated Cold Ischemia Time (CIT) \>=12 hours
• • 12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
• • 13. Patients with normal coagulation
• Exclusion Criteria:
• • 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• • 2. Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant
• • 3. Patients receiving enbloc kidneys
• • 4. Kidneys receiving normothermic perfusion
• • 5. Patients with a known pro-thrombotic disorder
• • 6. Patients with a history of thrombosis or hyper-coagulable state, excluding dialysis access clotting
• • 7. Body mass index (BMI) \>=40 kg/m\^2
• • 8. Patients with a history of Hereditary Angioedema or use of C1 esterase inhibitor (C1INH) containing products or recombinant C1INH within 15 days prior to study entry
• • 9. Patients with a known hypersensitivity to treatment with Berinert
• • 10. Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed
• • 11. Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin
• • 12. Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+ or anti-HBcore +)
• • 13. Any active infection
• • 14. Human immunodeficiency virus (HIV) infection
• • 15. Enrollment in another investigational trial
• • 16. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
• • 17. Current or planned use of immunomodulatory agents including but not limited to rituximab, belatacept, eculizumab, JAK inhibitors, anti-TNF agents
• • 18. Female participants who are pregnant or lactating
• • 19. Past or current medical problems, inclusive of mental health and substance abuse concerns, or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study