MNK-6105 for Patients With Cirrhosis and High Ammonia Levels Affecting Brain Function

Study Overview
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Brief Summary
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This study is for patients with cirrhosis and hepatic encephalopathy who are in the hospital. This means they have a high ammonia level which is affecting their brain function. All patients will receive the standard of (regular) care. Each will have an equal chance (like flipping a coin) of receiving the experimental drug or placebo along with the standard care. Each patient will have tests during the first 24 hours, receive treatment for up to 5 days, and have 30 days of follow-up.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of MNK6105 (an Intravenous Formulation of L-Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Hyperammonemia Associated With an Episode of Hepatic Encephalopathy

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: MNK-6105
* Drug: Placebo
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included, a patient must: Be the age of majority in their country (considered an adult) Be male or non-pregnant, non-lactating female Have OHE (Stage 2, 3, or 4) as a complication of cirrhosis Have been hospitalized within 24 hours before start of infusion (SOI) Receive at least 6 hours of SoC treatment Exclusion Criteria: Patients will be excluded if they have inadequate renal function or any other disease, laboratory value, or condition (including allergy, drug use or treatments) that per protocol or in the opinion of the investigator, might increase the risk of compromising: health or well-being of the patient safety of study staff analysis of results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MNK6105 + SoC<br>Participants will receive standard of care (SoC), along with MNK-6105 delivered by continuous intravenous (IV) infusion as follows: Loading dose: 20 g infused over 6 hours Intermediate dose: 15 g infused over 18 hours Maintenance dose: 15 g infused over 24 hours for up to 4 days | Drug: MNK-6105<br>* L-Ornithine Phenylacetate for IV infusion<br>* Other names: L-Ornithine Phenylacetate;Drug: Standard of Care<br>* Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.<br>* Other names: SoC;|
| Placebo Comparator: Placebo + SoC<br>Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days. | Drug: Placebo<br>* Matching placebo for IV infusion<br>* Other names: Matching Placebo;Drug: Standard of Care<br>* Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.<br>* Other names: SoC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a clinical response at Day 5 |  | at Day 5 (within 36 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients discharged 30 days after end of treatment. |  | at Day 35 (within 36 months) | 
| Number of patients readmitted to the hospital due to overt hepatic encephalopathy (OHE) 30 days after discharge. |  | 30 days after discharge (within 36 months) | 
| Number of patients with adverse events or deaths during the study |  | within 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overt HE diagnosis