miroliverELAP® for the Treatment of Acute Liver Failure: A Phase 1 Trial

A Phase 1 Prospective Study of the Miromatrix External Liver Assist Product (miroliverELAP®) for Liver Support in Adults With Acute Liver Failure.

The clinical trial will assess the safety of miroliverELAP for the treatment of acute liver failure, severe acute alcohol-associated hepatitis, or acute on chronic liver failure. miroliverELAP is an external liver assist combination product consisting of a single-use MIRO-001 bioengineered liver graft and an extracorporeal blood circuit. miroliverELAP Is intended to support the native (failed) liver for up to 48-hours of continuous treatment to allow time for liver recovery or to identify a transplantable liver.

This is a phase 1, open, single arm safety study of miroliverELAP for the treatment of acute liver failure (ALF), severe acute alcohol-associated hepatitis, or acute on chronic liver failure . Subjects who present with ALF, severe acute alcohol-associated hepatitis, or acute on chronic liver failure may be eligible for the study. Subjects will be treated with miroliverELAP continuously for 48 hours. The study will assess the safety of the miroliverELAP used to support liver function in an individual experiencing ALF, severe acute alcohol-associated hepatitis, or acute on chronic liver failure. Safety profile will be characterized by survival over the duration of therapy, tracking miroliverELAP-related adverse events, the proportion of subjects surviving 21-day post treatment initiation, and the difference in the values of specific biomarkers pre-treatment and at the time of treatment discontinuation; such as: albumin, ammonia, creatinine, INR, and lactate blood concentration. A minimum of 5 subjects will be treated for 48 hours and followed for 32 days. Up to 15 subjects may be enrolled in up to 8 study sites.

Inclusion Criteria:

1. 18 years to 80 years old at the time of signing the informed consent

2. Subject must:

   1. be deemed competent to consent by an independent qualified practitioner, or
   2. have consent given by a Legally Authorized Representative

3. Subject should be in the intensive care unit

4. Be diagnosed with 4.1. Acute Liver Failure defined as:

   1. INR ≥ 2.0, and
   2. Hepatic Encephalopathy Grade II-III (West Haven Criteria), and
   3. Less than 4 weeks (28 days) of disease duration 4.2. Severe Acute Alcohol-Associated Hepatitis as defined as:
   1. Hepatic Encephalopathy Grade I-III (West Haven Criteria), and
   2. Model for End-Stage Liver Disease (MELD) Score ≥ 20, and
   3. INR ≥ 2.0, and
   4. No overt evidence of cirrhosis 4.3. Acute on Chronic Liver Failure:

   1. Hepatic Encephalopathy Grade I-III (West Haven Criteria), and

   2. Model for End-Stage Liver Disease (MELD) Score ≥ 20, and

   3. INR ≥ 2.0,

      5. Subject is not a candidate for liver transplant and will not become a candidate in the event of worsening conditions.

Exclusion Criteria

1. Grade IV West Haven Encephalopathy Criteria

2. Previous liver transplant

3. Currently requires chronic hemodialysis (CRRT or other forms of continuous renal replacement are allowed).

4. Uncontrolled documented infection, hypotension, or refractory shock. This is defined as a need for a single vasopressor, or combination of vasopressors, that exceed a norepinephrine equivalent of 0.5 mcg/kg/min.

5. Liver injury due to trauma

6. Any current liver cancer

7. Currently on medications with a narrow therapeutic index

8. Platelet count < 40,000 μL

9. If the subject is intubated and has an acute lung injury

10. Experiencing a bleeding event, defined as:

    1. Active gastrointestinal or other overt bleeding event, or
    2. Hemoglobin drop > 3g/dL within the past 24 hours, or
    3. Received ≥ 3 units of red blood cell transfusion within the past 24 hours

11. Female that is currently pregnant, planning to be pregnant, or currently breastfeeding

12. Refusal to receive blood products