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

Phase 2

Not yet recruiting

• Conditions: Kidney Transplant
• Interventions: Biological: Berinert; Other: Placebo for Berinert

• Registration Number: NCT06919003
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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)

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-02
• Study First Submitted QC: 2025-04-02
• Last Update Submitted: 2025-04-02
• Study First Posted: 2025-04-09
• Last Update Posted: 2025-04-09
• Study Start: 2025-05-30
• Primary Completion: 2031-05-30
• Study Completion: 2032-05-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 180

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Berinert	Berinert	-
Saline	Placebo for Berinert	-

Primary Outcome Measures

Name	Time	Method
Difference between study arms in renal function	At 12-months post-transplantation	Measured as Estimated Glomerular Filtration Rate Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) in ml/min/1.73m\^2

Secondary Outcome Measures

Name	Time	Method
Comparison between the treated and control group of the full iBox score	At 12-months post-transplantation	The iBox scoring system is a composite biomarker panel. The full iBox scoring system consists of 4 elements all obtained 1-year post-transplant: a) eGFR (MDRD), b) DSA, c) urinary protein/creatine ratio, and d) histological abnormalities on a surveillance biopsy.
Incidence of biopsy proven acute rejection (BPAR)	At 12-months post-transplantation
Incidence of proteinuria	At 12-months post-transplantation	Measured as spot urine protein/creatinine \>1 g/g
Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA)	At 12-months post-transplantation	Defined as the incidence of de novo DSA on standard of care or protocol directed blood draws up to and including the 12-month protocol blood draw.
Incidence of Grade 3 or higher infections	At 12-months post-transplantation
Incidence of Grade 3 or higher intraoperative or postoperative hemorrhage	Within 4 weeks after transplantation
Incidence of thrombotic or thromboembolic events	Within 4 weeks after transplantation	Excluding superficial thrombophlebitis, catheter-related thrombosis and dialysis access thrombosis
Incidence of T cell mediated rejection (TCMR) that is steroid resistant	At 12-months post-transplantation
Incidence of TCMR that is BANFF grade 2 or higher	At 12-months post-transplantation
Incidence of antibody mediated rejection (ABMR)	At 12-months post-transplantation
Incidence of death	At 12-months post-transplantation
Incidence of Graft loss (including primary non function)	At 12-months post-transplantation

Trial Locations

Locations (4)

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States