Hepatic EncephalopathyPhase 3NCT04128462

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

A Phase 3 study testing MNK-6105 in people with Hepatic Encephalopathy, run by Mallinckrodt.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatic Encephalopathy
What is being tested?: MNK-6105
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 0 participants
Where: No sites listed yet
Study dates: Nov 2021to Jul 2025
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

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

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
Being tested: MNK-6105, Placebo, Standard of Care
Keywords: Overt HE diagnosis
Medical subject headings: Hepatic Encephalopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MNK-6105Drug
Also called L-Ornithine Phenylacetate
L-Ornithine Phenylacetate for IV infusion
PlaceboDrug
Also called Matching Placebo
Matching placebo for IV infusion
Standard of CareDrug
Also called SoC
Lactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.

Study groups in NCT04128462
Study group	Role	What they receive
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 Receives: 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. Receives: Drug: Placebo; Drug: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of patients with a clinical response at Day 5
Measured: at Day 5 (within 36 months)

Secondary outcomes (3)

Number of patients discharged 30 days after end of treatment.
Measured: at Day 35 (within 36 months)
Number of patients readmitted to the hospital due to overt hepatic encephalopathy (OHE) 30 days after discharge.
Measured: 30 days after discharge (within 36 months)
Number of patients with adverse events or deaths during the study
Measured: within 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2021Jul 2025

First posted16 Oct 2019
Study startNov 2021 (estimated)
Primary completionApr 2025 (estimated)
Study completionJul 2025 (estimated)

Why it stopped: Business Decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04128462
Sponsor's protocol ID: MNK61053106
Other IDs: 2019-001635-31, 2019
Status last verified: Sep 2021
First submitted: 14 Oct 2019
Last updated: 22 Sep 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruiting
Effect of Mini-Program Monitoring on Hepatic Encephalopathy in Post-TIPS Patients
Hepatic Encephalopathy, Liver Cirrhosis
Not yet recruitingPhase 4
Daridorexant for Sleep Disturbance in Adults With Liver Cirrhosis
Liver Cirrhosis, Sleep Disturbance
Not yet recruiting
Equivalence of Electronic vs Paper-based PHES in Diagnosing Hepatic Encephalopathy
Liver Cirrhosis, Hepatic Encephalopathy (HE)
Recruiting
4D-Flow MRI Assessment of Portal Hypertension and TIPS Outcomes in Cirrhosis
Cirrhosis, Portal Hypertension
Active, not recruitingPhase 1/2
RTX001 Autologous Engineered Macrophages for Liver Cirrhosis
End-stage Liver Disease (ESLD), Cirrhosis, Liver

All Hepatic Encephalopathy trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT04128462
Acronym / sponsor ID: MNK61053106
Conditions: Hepatic Encephalopathy
Keywords: Overt HE diagnosis
Phase: Phase 3
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Business Decision
Enrolment: 0 participants (actual)
Lead sponsor: MallinckrodtIndustry (pharma, biotech, devices)
Study start: Nov 2021 (estimated)
Primary completion: Apr 2025 (estimated)
Study completion: Jul 2025 (estimated)
First posted: 16 Oct 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
MNK6105 + SoC	Experimental	Drug: MNK-6105, Drug: Standard of CareParticipants 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 comparator	Drug: Placebo, Drug: Standard of CareParticipants will receive SoC, along with continuous IV infusion of matching placebo for 5 days.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MNK-6105Also: L-Ornithine PhenylacetateL-Ornithine Phenylacetate for IV infusion	Drug	MNK6105 + SoC
PlaceboAlso: Matching PlaceboMatching placebo for IV infusion	Drug	Placebo + SoC
Standard of CareAlso: SoCLactulose ± rifaximin as SoC treatment for overt HE should be administered per the clinical judgement of the investigator and usual institutional practice.	Drug	MNK6105 + SoC, Placebo + SoC

Primary outcome

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

3 secondary outcomes

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

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
Individual participant dataSharing planned: No

Related trials for Hepatic Encephalopathy

Not yet recruiting
Effect of Mini-Program Monitoring on Hepatic Encephalopathy in Post-TIPS Patients
Hepatic Encephalopathy, Liver Cirrhosis
Not yet recruitingPhase 4
Daridorexant for Sleep Disturbance in Adults With Liver Cirrhosis
Liver Cirrhosis, Sleep Disturbance
Not yet recruiting
Equivalence of Electronic vs Paper-based PHES in Diagnosing Hepatic Encephalopathy
Liver Cirrhosis, Hepatic Encephalopathy (HE)
Recruiting
4D-Flow MRI Assessment of Portal Hypertension and TIPS Outcomes in Cirrhosis
Cirrhosis, Portal Hypertension
Active, not recruitingPhase 1/2
RTX001 Autologous Engineered Macrophages for Liver Cirrhosis
End-stage Liver Disease (ESLD), Cirrhosis, Liver

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Team Leader study director

Mallinckrodt

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MNK-6105 in people with Hepatic Encephalopathy, run by Mallinckrodt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with a clinical response at Day 5 (time frame: at Day 5 (within 36 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04128462.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2021.