Berinert (C1INH) vs Placebo for DGF/IRI

NCT04696146 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 469
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II double-blind, randomized, placebo-controlled study assessing safety and limited efficacy of intraoperative C1INH (500U/kidney) vs. Placebo administered into the graft renal artery 1-2 hours prior to implantation in adult subjects receiving a deceased donor kidney allograft considered high-risk for development of DGF (KDPI\>80). Once eligible patients are identified, consented, and have an acceptable kidney transplant offer, they will be randomized by the Cedars-Sinai Research Pharmacy to receive study drug vs. placebo. Drug and placebo will be prepared by the Cedars-Sinai Research Pharmacy and conveyed to the operating room in a blinded manner. The drug will be administered by the transplant surgeon in the OR in a blinded manner.

Conditions

End Stage Renal Disease; Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (3)

• Need for Dialysis in the First 30 Days Post-transplant

  The percentage of patients enrolled who require at least one session of dialysis in the first 30 days post transplant.

  30 days

• Renal Function 6 Months

  eGFR at 6M post-transplant

  6 months

• Graft Survival 6 Months

  Number of participants with graft survival at 6 Months

  6 months

Secondary Outcomes (2)

• Rejection Episodes at 6 Months

  Month 6

• Development of Donor Specific Antibodies (DSA) at 6 Months

  Month 6

Other Outcomes (1)

• Adverse Events in the Study Population

  Month 6

Study Arms (2)

Berinert

EXPERIMENTAL

Berinert 500 units

Drug: Berinert

Placebo

PLACEBO COMPARATOR

Normal Saline in identical volume to Berinert

Drug: Placebo

Interventions

Berinert DRUG

Intrarenal dose of 500 U of Berinert

Also known as: C1 Esterase Inhibitor (C1INH)

Berinert

Placebo DRUG

Normal Saline placebo

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men or women (18-70 years of age) who are on chronic dialysis therapy and acceptable candidates for receipt of a kidney transplant.
• Recipients who are ABO compatible with donor allograft
• Understand and sign a written inform consent prior to any study specific procedure
• Women of childbearing potential must have a negative pregnancy test prior to randomization, and must be on an acceptable form of birth control.
• AND one of the below criteria:
• a)Recipients of kidney allograft from KDPI \>80 donors b)Recipients of kidney allograft from DCD donors c)Recipients of kidney allograft with CIT \> 24 hours d)Recipients of kidney allograft from donor on HD/CRRT prior to death/procurement e)Recipients of kidney allograft with donor terminal creatinine SCr ≥3.0 mg/dL f)Patient risk a total risk index score of \>/=3

You may not qualify if:

• Patients with a known pro-thrombotic disorder. (eg. Factor V Leiden)
• Patients with a history of thrombosis or hypercoagulable state, excluding access clotting.
• Patients with a history of administration of C1INH containing products or recombinant C1INH within 15 days prior to study entry.
• Patients with a known hypersensitivity to treatment with C1INH.
• Patients with an abnormal coagulation function. (INR\>2, PTT\> 50, PLT\<60,000)who are not on anti-coagulation.
• Patients with known active presence of malignancies.
• Patients who arePCR positive for Hep B, Hep C, or HIV.
• Recipients of pre-emptive kidney transplantation.
• All zero mismatch kidneys.
• Recipients of multi-organ transplants. (kidney and any other organ)
• Recipients of kidney allograft that was on pump preservation for any period prior to transplantation.
• Recipients of kidney allograft from a living donor.13)Female subjects who are pregnant or lactating.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• OneLegacy Foundation: collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Huang E, Ammerman N, Vo A, Hou J, Kumar S, Badash N, Falk B, Hernando K, Gillespie M, Kim IK, Lim K, Najjar R, Peng A, Shin B, Steggerda JA, Todo T, Brennan TV, Voidonikolas G, Wisel SA, Heeger PS, Jordan SC. Back-table intra-arterial administration of C1 esterase inhibitor to deceased donor kidney allografts improves posttransplant allograft function: Results of a randomized double-blind placebo-controlled clinical trial. Am J Transplant. 2025 Sep;25(9):1926-1939. doi: 10.1016/j.ajt.2025.05.003. Epub 2025 May 9.

  PMID: 40349965 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Renal Insufficiency, Chronic

Interventions

Complement C1 Inhibitor Protein; Saline Solution

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Noriko Ammerman
• Organization: Cedars-Sinai Medical Center

noriko.ammerman@cshs.org

3102488186

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Once eligible patients are identified, consented, and have an acceptable kidney transplant offer, they will be randomized by the Cedars-Sinai Research Pharmacy to receive study drug vs. placebo. Drug and placebo will be prepared by the Cedars-Sinai Research Pharmacy and conveyed to the operating room in a blinded manner. The drug will be administered by the transplant surgeon in the OR in a blinded manner.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Nephrology and Transplant Immunology

Model Details: Intraoperative C1INH (500U/kidney) vs. Placebo administered into the graft renal artery 1-2 hours prior to implantation in adult subjects receiving a deceased donor kidney allograft considered high-risk for development of DGF (KDPI\>80). Patients will be randomized in a 1:1 manner

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: January 6, 2021
• Study Start: March 3, 2021
• Primary Completion: July 31, 2022
• Study Completion: October 31, 2024
• Last Updated: December 4, 2024
• Results First Posted: September 29, 2023

Record last verified: 2024-11

Locations

US (1)