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

Sponsor

Mallinckrodt (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04128462

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: MNK-6105 Drug: Placebo Drug: Standard of Care	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

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: Placebo Matching placebo for IV infusion Other Names: Matching Placebo 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

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: Placebo

Matching placebo for IV infusion

Other Names:

Matching Placebo

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

Outcome Measures

Primary Outcome Measures

Number of patients with a clinical response at Day 5 [at Day 5 (within 36 months)]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Mallinckrodt

Investigators

Study Director: Clinical Team Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mallinckrodt

ClinicalTrials.gov Identifier:

NCT04128462

Other Study ID Numbers:

MNK61053106
2019-001635-31

First Posted:

Oct 16, 2019

Last Update Posted:

Sep 22, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Mallinckrodt

Overt HE diagnosis

Additional relevant MeSH terms:

Hepatic Encephalopathy

Brain Diseases

Phenylacetic acid

Study Results

No Results Posted as of Sep 22, 2021