Pilot Trial of Eculizumab Therapy to Reduce Preservation Injury in Human Macrosteatotic Liver Transplantation

NCT03468140 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: 2000021373
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The number of liver transplants that can be performed is limited by the availability of organs. Livers that are steatotic (i.e., infiltrated by triglycerides and other fatty substances) are usually not used for transplants, due to increased risk of adverse events and deaths post-transplant. The investigators propose administering eculizumab to patients receiving macrosteatotic liver transplants and hypothesize that doing so will mitigate post-surgical adverse outcomes.

Conditions

End Stage Liver Disease

Outcome Measures

Primary Outcomes (1)

• Degree of Hepatocellular Injury

  Hepatocellular injury will be assessed by aminotranferase (AST) that will be measured for 7 days following transplant.

  Days 1-7 following liver transplant.

Secondary Outcomes (5)

• Alanine transaminase (ALT) recovery time

  Days 1-7 following liver transplant.

• Seven-day peak post-transplant (GCT)

  Days 1-7 following liver transplant.

• Gamma-glutamyl transpeptidase (GCT) recovery time

  Days 1-7 following liver transplant.

• International Normalized Ratio (INR) recovery time

  Days 1-7 following liver transplant.

• Seven-day peak post-transplant creatinine

  Days 1-7 following liver transplant.

Other Outcomes (9)

• One-year incidence of biopsy-proven acute transplant rejection

  One year from date of transplant

• Post-transplant blood loss

  One year from date of transplant

• One-year all-cause mortality

  One year from date of transplant

Study Arms (2)

Current end stage liver disease patients

EXPERIMENTAL

Eculizumab

Drug: Eculizumab

Historical controls

OTHER

The Ochsner database will be used to obtain 5 historical matches for each study participant. Matching criteria for each patient will include: 1) gender; 2) (MELD) Score ± 5; 3) age ± 5 years; 4) body mass index (BMI) ± 5 kg/m2; 5) donor macrosteatosis ± 5%; and 6) CIT± 3 hours.

Other: No intervention

Interventions

Eculizumab DRUG

Eculizumab will be given at a dose of 1200mg diluted in 0.9% sodium chloride (NaCl) to 5mg/mL for a total volume of 240 mL administered by IV infusion over 25-45 minutes in the anhepatic-phase during the transplant procedure, and a second dose of 900mg diluted in 0.9% NaCl to 5mg/mL for a total volume of 180 mL administered by IV infusion over 25-45 minutes will be given 24 hours following the first dose.

Current end stage liver disease patients

No intervention OTHER

Historical control arm

Historical controls

Eligibility Criteria

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

You may qualify if:

• Age\>18, weight\>40kg
• Recipients of first liver transplant
• Biopsy proven macrosteatosis of \> or = 20%
• Cold ischemia time \< 8 hours
• Recipients of brain-dead deceased donors

You may not qualify if:

• Dual organ transplants
• ABO incompatible
• Meningococcal vaccination refusal
• Dual barrier contraception refusal
• Recipients with acute liver failure
• Recipients with Hepatitis B or C viral loads
• Physiological MELD Score\>35
• Donor liver biopsy showing combined Microsteatosis+Macrosteatosis\>70%

Sponsors & Collaborators

• Yale University: lead
• Ochsner Health System: collaborator
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

MeSH Terms

Conditions

End Stage Liver Disease

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Sanjay Kulkarni, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery (Transplant) and of Medicine (Nephrology)

Model Details: Five end-stage liver disease (ESLD) patients will be matched to 5 historical controls.

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 16, 2018
• Study Start: October 1, 2021
• Primary Completion: April 30, 2023
• Study Completion: December 31, 2023
• Last Updated: April 8, 2021

Record last verified: 2021-04

Locations

US (1)