Single intragraft injection of C1 esterase inhibitor to improve deceased-donor kidney transplant outcomes

Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (RTB-021)

This trial will test whether injecting Berinert into deceased-donor kidneys before transplant helps adults on dialysis who are receiving high-risk deceased-donor kidney transplants have better kidney function over the first year.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Drugs / interventions: rituximab, eculizumab
• Locations: 4 sites (Los Angeles, California and 3 other locations)
• Trial ID: NCT06919003 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial that gives a single intrarenal artery injection of Berinert (C1 esterase inhibitor) into donor kidneys immediately prior to transplantation. Adults on chronic dialysis who are listed for high-risk deceased-donor kidney transplants and meet compatibility and antibody criteria are randomized to Berinert or an identical-appearing placebo. The primary outcome is recipient kidney function at 12 months measured by eGFR (CKD-EPI), with safety and other graft outcomes also tracked. The trial is conducted at multiple U.S. transplant centers and follows participants through the first post-transplant year.

Who should consider this trial

Good fit: Adults on chronic dialysis who are awaiting a compatible high-risk deceased-donor kidney transplant, have a negative crossmatch and no donor-specific anti-HLA antibodies, and can give informed consent are the intended participants.

Not a fit: Living-donor recipients, patients with a positive crossmatch or significant donor-specific antibodies, or those who cannot meet the study compatibility or contraception requirements are unlikely to be eligible or benefit from this intervention.

Why it matters

Potential benefit: If successful, the treatment could improve one-year kidney function and reduce early graft dysfunction or need for dialysis after high-risk deceased-donor transplants.

How similar studies have performed: Preclinical work and small clinical reports suggest complement inhibition can reduce ischemia–reperfusion injury, but intragraft C1 esterase inhibitor injection in high-risk deceased-donor kidneys is relatively novel and not yet proven in larger trials.

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. Recipients of kidneys that received in situ normothermic regional perfusion in the donor are eligible. Kidneys that received normothermic machine perfusion after organ procurement (ex situ normothermic perfusion) are not eligible (See Exclusion #4)
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. Prior autologous transplant is allowed
3. Patients receiving enbloc kidneys
4. Kidneys that received ex vivo normothermic machine perfusion after procurement. Kidneys that received in situ normotherimic regional perfusion in the donor are eligible (see Inclusion #10)
5. Patients with a known pro-thrombotic disorder
6. Patients with a history of thrombosis or hyper-coagulable state, excluding dialysis access clotting or other superficial vein thrombosis not requiring long-term systemic treatment
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, renal cell carcinoma stage T1N0M0 that has been treated with nephrectomy, 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)+); patients with HbcAB+ are eligible if HBV PCR is negative
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
20. History of any stroke (including ischemic, hemorrhagic, or embolic) within the previous 6 months

Where this trial is running

Los Angeles, California and 3 other locations

• Cedars Sinai Medical Center — Los Angeles, California, United States (Recruiting)
• Northwestern Memorial Hospital — Chicago, Illinois, United States (Recruiting)
• Kansas University Medical Center — Kansas City, Kansas, United States (Recruiting)
• Montefiore Medical Center — The Bronx, New York, United States (Recruiting)

Conditions Kidney Transplant; Kidney transplant; Deceased donor; Intragraft injection; C1 esterase inhibitor