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

Phase 3

Withdrawn

• Conditions: Hepatic Encephalopathy
• Interventions: Drug: MNK-6105; Drug: Placebo; Drug: Standard of Care

• Registration Number: NCT04128462
• Lead Sponsor: Mallinckrodt

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-14
• Study First Submitted QC: 2019-10-14
• Study First Posted: 2019-10-16
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-16
• Last Update Posted: 2021-09-22
• Study Start: 2021-11
• Primary Completion: 2025-04
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MNK6105 + SoC	MNK-6105	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
MNK6105 + SoC	Standard of Care	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
Placebo + SoC	Placebo	Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.
Placebo + SoC	Standard of Care	Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.

Primary Outcome Measures

Name	Time	Method
Number of patients with a clinical response at Day 5	at Day 5 (within 36 months)

Secondary Outcome Measures

Name	Time	Method
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