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

NCT06919003 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAIT RTB-021
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 4

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)

Conditions

Kidney Transplant

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Comparison between the treated and control group of the full iBox score

  At 12-months post-transplantation

• Incidence of biopsy proven acute rejection (BPAR)

  At 12-months post-transplantation

• Incidence of proteinuria

  At 12-months post-transplantation

• Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA)

  At 12-months post-transplantation

• Incidence of Grade 3 or higher infections

  At 12-months post-transplantation

Study Arms (2)

Berinert

EXPERIMENTAL

Biological: Berinert

Saline

PLACEBO COMPARATOR

Other: Placebo for Berinert

Interventions

Berinert BIOLOGICAL

Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft

Also known as: C1 esterase inhibitor, C1INH

Berinert

Placebo for Berinert OTHER

Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft

Saline

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be able to understand and provide informed consent
• Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
• Recipients who are ABO compatible with donor allograft
• Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
• Female participants of childbearing potential must have a negative pregnancy test upon study entry
• 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
• 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
• 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
• Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
• Anticipated Cold Ischemia Time (CIT) \>=12 hours
• Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours
• Patients with normal coagulation

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant. Prior autologous transplant is allowed
• Patients receiving enbloc kidneys
• Patients with a known pro-thrombotic disorder
• 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
• Body mass index (BMI) \>=40 kg/m\^2
• 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
• Patients with a known hypersensitivity to treatment with Berinert
• Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed
• 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
• Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+); patients with HbcAB+ are eligible if HBV PCR is negative
• Any active infection
• Human immunodeficiency virus (HIV) infection
• Enrollment in another investigational trial
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467-2401, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study is a double-blind, placebo-controlled study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): May 30, 2031
• Study Completion (Estimated): May 30, 2032
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)