Clinical trial NCT06919003: Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (IMPROVE TRIAL)
Official title: Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (RTB-021)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Kidney Transplant
Keywords: Kidney transplant
Deceased donor
Intragraft injection
C1 esterase inhibitor
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2025-04-09
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out if Berinert can improve kidney function in the first year after transplant and to find out what effects, good or bad, Berinert will have in the kidney recipient. This research study will compare Berinert to placebo. The placebo looks exactly like Berinert but does not contain any active drug. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons. Neither you or the study doctor can choose or know which group is assigned.

The primary objective is to test whether intrarenal artery C1 esterase inhibitor (C1INH) injection into the donor kidney prior to transplantation improves kidney function in recipients of high risk, deceased donor kidney transplants as measured by 12-month Estimated Glomerular Filtration Rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI)


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

Primary outcomes:
measure: Difference between study arms in renal function
timeFrame: At 12-months post-transplantation
Secondary outcomes:
measure: Comparison between the treated and control group of the full iBox score
timeFrame: At 12-months post-transplantation
measure: Incidence of biopsy proven acute rejection (BPAR)
timeFrame: At 12-months post-transplantation
measure: Incidence of proteinuria
timeFrame: At 12-months post-transplantation
measure: Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA)
timeFrame: At 12-months post-transplantation
measure: Incidence of Grade 3 or higher infections
timeFrame: At 12-months post-transplantation
measure: Incidence of Grade 3 or higher intraoperative or postoperative hemorrhage
timeFrame: Within 4 weeks after transplantation
measure: Incidence of thrombotic or thromboembolic events
timeFrame: Within 4 weeks after transplantation
measure: Incidence of T cell mediated rejection (TCMR) that is steroid resistant
timeFrame: At 12-months post-transplantation
measure: Incidence of TCMR that is BANFF grade 2 or higher
timeFrame: At 12-months post-transplantation
measure: Incidence of antibody mediated rejection (ABMR)
timeFrame: At 12-months post-transplantation
measure: Incidence of death
timeFrame: At 12-months post-transplantation
measure: Incidence of Graft loss (including primary non function)
timeFrame: At 12-months post-transplantation
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Peter S Heeger, MD
role: STUDY_CHAIR
affiliation: Cedars-Sinai Medical Center
name: Sindhu Chandran, MBBS, MD
role: STUDY_CHAIR
affiliation: Cedars-Sinai Medical Center
name: Stanley Jordan, MD
role: STUDY_CHAIR
References: