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

NCT04128462 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: MNK610531062019-001635-31
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatic Encephalopathy

Keywords

Overt HE diagnosis

Outcome Measures

Primary Outcomes (1)

• Number of patients with a clinical response at Day 5

  at Day 5 (within 36 months)

Secondary Outcomes (3)

• 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

Study Arms (2)

MNK6105 + SoC

EXPERIMENTAL

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; Drug: Standard of Care

Placebo + SoC

PLACEBO COMPARATOR

Participants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.

Drug: Placebo; Drug: Standard of Care

Interventions

MNK-6105 DRUG

L-Ornithine Phenylacetate for IV infusion

Also known as: L-Ornithine Phenylacetate

MNK6105 + SoC

Placebo DRUG

Matching placebo for IV infusion

Also known as: Matching Placebo

Placebo + SoC

Standard of Care DRUG

Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.

Also known as: SoC

MNK6105 + SoC; Placebo + SoC

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mallinckrodt: lead

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Clinical Team Leader

  Mallinckrodt

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 16, 2019
• Study Start: November 1, 2021
• Primary Completion: April 1, 2025
• Study Completion: July 1, 2025
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share