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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant
• Intervention / Treatment: Biological: Berinert; Other: Placebo for Berinert

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
      • Contact: Tillie Morrisette; Phone Number: 424-315-1316; Email: tillie.morrisette@cshs.org
      • Contact: Andrea Calderon; Phone Number: 310-423-2319; Email: Andrea.Calderon@cshs.org
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Contact: Laura Adams; Phone Number: 312-694-0242; Email: laura.adams@nm.org
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Kansas University Medical Center
      • Contact: Adam Schooey; Phone Number: 913-588-1699; Email: aschooley@kumc.edu
  • New York
    • The Bronx, New York, United States, 10467-2401
      • Recruiting
      • Montefiore Medical Center
      • Contact: Harith Raees; Phone Number: 929-285-4339; Email: hraees@montefiore.org

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline	Other: Placebo for Berinert; Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft
Experimental: Berinert	Biological: Berinert; Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft; Other Names: C1INH; C1 esterase inhibitor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison between the treated and control group of the full iBox score	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.	At 12-months post-transplantation
Incidence of biopsy proven acute rejection (BPAR)		At 12-months post-transplantation
Incidence of proteinuria	Measured as spot urine protein/creatinine >1 g/g	At 12-months post-transplantation
Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA)	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.	At 12-months post-transplantation
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	Excluding superficial thrombophlebitis, catheter-related thrombosis and dialysis access thrombosis	Within 4 weeks after transplantation
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

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Peter S Heeger, MD, Cedars-Sinai Medical Center; Study Chair: Sindhu Chandran, MBBS, MD, Cedars-Sinai Medical Center; Study Chair: Stanley Jordan, MD, Cedars-Sinai Medical Center

Publications and helpful links

Helpful Links

• Division of Allergy, Immunology, and Transplantation (DAIT)
• National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2025
• Primary Completion (Estimated): May 30, 2031
• Study Completion (Estimated): May 30, 2032

Study Registration Dates

• First Submitted: April 2, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Kidney transplant; C1 esterase inhibitor; Deceased donor; Intragraft injection
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Carbohydrates; Immunoproteins; Blood Proteins; Glycoproteins; Glycoconjugates; Serpins; Complement C1 Inactivator Proteins; Complement Inactivator Proteins; Complement System Proteins; Complement C1 Inhibitor Protein
• Other Study ID Numbers: DAIT RTB-021

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