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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: MNK-6105; Drug: Standard of Care; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. health or well-being of the patient
2. safety of study staff
3. analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MNK6105 + SoC; 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; L-Ornithine Phenylacetate for IV infusion; Other Names: L-Ornithine Phenylacetate; Drug: Standard of Care; Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.; Other Names: SoC
Placebo Comparator: Placebo + SoC; Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.	Drug: Standard of Care; Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.; Other Names: SoC; Drug: Placebo; Matching placebo for IV infusion; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: October 14, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Overt HE diagnosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Phenylacetic acid
• Other Study ID Numbers: MNK61053106; 2019-001635-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No