CINRYZE as a Donor Pre-treatment Strategy in Kidney Recipients of KDPI>60%

NCT02435732 | Unknown Phase 1 DMC FDA Drug

• 4 other identifiers: 2015-0195A539742SMPH/SURGERY/TRANSPLANTProtocol Version 5/28/2018
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

Brief Summary

Limiting brain death-induced organ injury through a systemic anti- inflammatory medical management should allow for improvement in the quality of transplanted organs, and as a result, clinical improvement in post-transplant outcomes represented by a decrease in the incidence of delayed graft function (DGF) after transplantation. The specific aim is to evaluate the effect of C1INH (CINRYZE) as a donor pre-treatment strategy to decrease systemic inflammation and decrease the incidence of DGF in Expanded Criteria Donors (ECD), currently identified as donors with Kidney Donor Profile Index (KDPI) greater than or equal to 60%.

Conditions

Kidney Failure

Outcome Measures

Primary Outcomes (1)

• Lowest dose that will allow at least an 80% decrease in the activity of classic pathway and MBL pathway of complement in brain death donors with KDPI over 60%, with the purpose of reducing the incidence of delayed graft function.

  Assessment of graft function

  over a 12 month period

Secondary Outcomes (5)

• Donor Pharmacokinetics: plasma concentrations and Area under the Curve (AUC) for CINRYZE

  At various timepoints within first 24 hours

• Rate of of DGF in kidney transplantation from ECD brain death donors

  Within 6 hours of brain death

• Level of suppression of the classical and MBL pathways

  Within 6 hours of brain death

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Day of Transplant: first 24 hours, days 2-7, weeks 2,3,8, month 3, 6, 12

• Levels of complement activation after brain death in donors treated with C1INH

  Within 6 hours of brain death

Study Arms (3)

Control group

PLACEBO COMPARATOR

Standard donor management + vehicle treatment (n=9)- placebo saline solution

Drug: Placebo saline solution

CINRYZE 200 U/Kg IV

EXPERIMENTAL

Intervention is CINRYZE 200 U/Kg IV single dose

Drug: Placebo saline solution; Drug: CINRYZE

200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV

EXPERIMENTAL

CINRYZE 200 units/kg IV single dose with Heparin at 20 units/kg/h IV maintenance until organ recovery

Drug: Placebo saline solution; Drug: Heparin; Drug: CINRYZE

Interventions

Placebo saline solution DRUG

saline solution

200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV; CINRYZE 200 U/Kg IV; Control group

Heparin DRUG

Added to the one of the arms receiving 200U/kg dose of CINRYZE

200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV

CINRYZE DRUG

200U/kg IV dose with or without heparin, or 500U/kg IV dose

Also known as: C1INH

200 units/kg IV CINRYZE with Heparin 20 U/kg/h IV; CINRYZE 200 U/Kg IV

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients receiving a kidney from a donor with KDPI\>60%
• Provide written informed consent.
• Accepted for renal transplantation due to end stage renal disease (Chronic Kidney Disease Stage V).
• Recipient of a first or second renal transplant.
• For second renal transplantation, minimum 3 months since the loss of the first transplanted kidney.
• At least 18 years of age:
• If female, patient must be/have:
• Post-menopausal, defined as the absence of menses for at least one year (serum FSH ≥20I U/L can also be measured according to local practice), OR Surgically sterile, defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR Using an effective means of contraception (per Appendix 1) that is planned to continue for the duration of the study (one year), AND negative urine pregnancy test if the patient is capable of providing a urine sample. If not capable to provide urine sample, serological pregnancy test will be perform.
• Female patients of childbearing potential who are anuric must have a serum pregnancy test.
• If male, patient must:
• Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue for the duration of the study (6 months).
• Agree not to donate sperm until 6 months after dosing.
• Patients must be willing to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
• Provide written informed consent.
• Accepted for liver transplantation

You may not qualify if:

• Use of an investigational drug in the 30 days before surgery.
• Participation in any other research study (drug or non-drug) without prior approval from the Medical Monitor.
• Known hypersensitivity to human monoclonal antibodies or any of the study drug excipients.
• Previous hypersensitivity to basiliximab, Campath-1H or antithymocyte globulin (ATG)
• History of or known HIV, HBV (surface antigen), or HCV positivity
• History of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin, or cervical intraepithelial neoplasia.
• Scheduled to undergo multi-organ transplantation.
• Presence of clinically significant infections requiring continued therapy.
• Positive screening for active tuberculosis.
• Existence of any surgical or medical condition, other than the current transplantation which, in the opinion of the investigator, might significantly alter the distribution, metabolism or excretion of study medication.
• History or presence of a medical condition or disease that in the investigator's assessment would place the patient at an unacceptable risk for study participation.
• Lactating or pregnant woman.
• Patient institutionalized by administrative or court order.
• HLA or ABO incompatible kidney defined as a positive cytotoxic crossmatch, positive mean fluorescent intensity beyond the acceptable parameters by the institution, or flow crossmatch-based assay that is positive (for kidney recipients only)
• Donor who is known to have received an investigational drug for I-R injury or graft rejection (immunosuppressant) in the 48H prior to organ recovery

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Shire: collaborator

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Heparin; SERPING1 protein, human

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Luis Fernandez, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Fernandez, MD

CONTACT

(608) 263-9903; luisf@surgery.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: May 6, 2015
• Study Start: December 1, 2020
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2022
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share