MW189 for Brain Bleed

(BEACH Trial)

Recruiting at 10 trial locations

Overseen By Andrew Carlson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Immunosuppressants, Anti-inflammatories

Disqualifiers: Pregnancy, Liver disease, Kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 5 days

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MW189 to determine its safety and tolerability in individuals who have experienced a brain bleed, known as an intracerebral hemorrhage (ICH). Participants will receive either MW189 or a placebo (a harmless substance with no active ingredient) within 24 hours of symptom onset. The trial seeks individuals who have had a sudden, non-traumatic ICH and are stable after treatment to reverse any blood thinners. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have used chronic immunosuppressants or anti-inflammatory drugs (except low-dose aspirin) in the past 7 days.

Is there any evidence suggesting that MW189 is likely to be safe for humans?

Research has shown that MW189 underwent safety testing in earlier studies. In healthy adults, MW189 was well tolerated, with no major safety concerns. Participants received both single and multiple doses of up to 0.25 mg/kg without significant issues. This suggests MW189 might be safe for human use, although it has not been tested in individuals with brain bleeds until now. Notably, this is the first time MW189 is being tested in patients with intracerebral hemorrhage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain bleeds, which often focus on managing symptoms and preventing complications, MW189 targets the inflammatory response in the brain. This is exciting because MW189 is designed to be administered quickly—within 24 hours of symptom onset—and repeatedly over a short period, potentially reducing brain damage more effectively. Researchers are particularly interested in its unique mechanism of action, which aims to calm the inflammatory processes that exacerbate brain injury, offering a novel approach that could lead to better outcomes for patients.

What evidence suggests that MW189 might be an effective treatment for brain bleed?

Research has shown that MW189, which participants in this trial may receive, might help treat brain bleeds by reducing inflammation and swelling in the brain. Studies indicate that MW189 lowers levels of harmful proteins linked to inflammation while boosting helpful ones. In animal studies, it reduced brain swelling and aided recovery after brain injuries. This treatment is designed to enter the brain and directly target inflammation, which is thought to support healing. Early results in humans also show promise in reducing signs of brain inflammation. ^{1 6 7 8 9}

Who Is on the Research Team?

Linda Van Eldik

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed diagnosis of spontaneous, non-traumatic brain bleeding (ICH) who can start treatment within 24 hours after symptoms begin. They must have a certain level of consciousness and stable blood pressure, not be pregnant or lactating, and cannot have severe liver or kidney issues or infections.

Inclusion Criteria

You had a magnetic resonance spectroscopy score between 0 and 2 before becoming sick.

I am on blood thinners but can stop them if I have symptoms of a brain bleed.

I can start the trial treatment within 24 hours after my stroke symptoms began.

Exclusion Criteria

I do not have severe liver or kidney disease.

You are expected to stop life-sustaining treatments within the first week after joining the study.

In the opinion of the investigator, patient has a condition that could interfere with the proposed treatment or unacceptably increase the individual's risk by participating in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

MW189 or placebo is administered within 24 hours of symptom onset and every 12 hours for up to 5 days

5 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MW189

Trial Overview

The BEACH study is testing the safety of MW189 compared to saline in patients with brain hemorrhage. It's a phase 2a pilot study where participants are randomly chosen to receive either MW189 or saline to see how well they tolerate it.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

MW189 (0.25 mg/kg) is administered within 24 hours of symptom onset and every 12 hours for up to 5 days (10 total doses) or until discharge (if earlier than 5 days)

Group II: Control Placebo Group 1 Intervention

Administration of saline within 24 hours of symptom onset and every 12 hours for up to 5 days (10 total doses) or until discharge (if earlier than 5 days)

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

University of Kentucky

Collaborator

Trials

198

Recruited

224,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 64 patients with traumatic brain stem hemorrhage (TBH) over 5 years, the most common site of hemorrhage was the midline rostral anterior brain stem, which had a surprisingly high survival rate of 71%.

Patients with brain stem hemorrhage associated with transtentorial herniation had a 100% mortality rate, highlighting the severity of this injury pattern compared to others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute traumatic midbrain hemorrhage: experimental and clinical observations with CT. Meyer, CA., Mirvis, SE., Wolf, AL., et al.[2016]

In a case study of a 35-year-old woman who suffered traumatic basal subarachnoid hemorrhage (TBSAH) after being punched in the neck, autopsy revealed a massive hemorrhage at the base of the brain with no detectable tears in the vertebro-basilar arteries.

The source of the TBSAH was likely from hemorrhagic cerebellar contusions, indicating that severe neck trauma can lead to significant brain injuries even without direct vascular damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar contusions as a possible cause of traumatic basal subarachnoid hemorrhage: a case report. Chen, JH., Ishikawa, T., Michiue, T., et al.[2010]

In a study of six patients with partial tegmental pontine hemorrhages, common symptoms included miosis, gaze paresis, facial paralysis, and sensory loss, with most patients being hypertensive.

All patients survived with mild long-term effects, particularly oculomotor disturbances, and factors like smaller hemorrhage size, unilateral injury, and lack of coma were associated with better recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tegmental pontine hemorrhages: clinical features and prognostic factors. Lancman, M., Norscini, J., Mesropian, H., et al.[2016]

Transplant recipients who experience brain stem death can be safely used as organ donors, as demonstrated by two case reports where liver grafts from such donors resulted in successful transplants with recipients thriving for over 22 months.

Chronic exposure to immunosuppressive drugs does not automatically disqualify transplant patients from being organ donors, suggesting that these organs can still be viable for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of grafts procured from organ transplant recipients. Arvieux, C., Cornforth, B., Gunson, B., et al.[2019]

This case study presents a unique instance of traumatic basal subarachnoid hemorrhage (TBSAH) resulting from cerebellar contusions, which is a rare occurrence, particularly linked to a coup injury from blunt trauma.

The autopsy of a 55-year-old woman revealed massive subarachnoid hemorrhage without any common sources like ruptured aneurysms or vascular malformations, suggesting that cerebellar contusions can be a significant but overlooked cause of TBSAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Traumatic basal subarachnoid hemorrhage suspected to have been caused by contrecoup cerebellar contusions: a case report. Sato, T., Tsuboi, K., Nomura, M., et al.[2014]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10959780/

A Phase 2a Study of MW189 in Patients with Acute ...

A novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes.

2.

accp1.onlinelibrary.wiley.com

accp1.onlinelibrary.wiley.com/doi/full/10.1002/cpdd.795

First‐in‐Human Studies of MW01‐6‐189WH, a Brain ...

MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 ...

3.

clinicaltrials.gov

clinicaltrials.gov/ct2/show/NCT05020535?draw=2&rank=1

Biomarker and Edema Attenuation in IntraCerebral ...

In animal models of acute brain injuries such as ICH and Traumatic Brain Injury (TBI), MW189 attenuates neuroinflammation, reduces cerebral edema, and improves ...

4.

researchgate.net

researchgate.net/publication/340495199_First-in-Human_Studies_of_MW01-6-189WH_a_Brain-Penetrant_Antineuroinflammatory_Small-Molecule_Drug_Candidate_Phase_1_Safety_Tolerability_Pharmacokinetic_and_Pharmacodynamic_Studies_in_Healthy_Adult_Vo

(PDF) First‐in‐Human Studies of MW01‐6‐189WH, a Brain ...

MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF‐α and higher levels of the anti‐inflammatory cytokine IL‐10 ...

5.

uknowledge.uky.edu

uknowledge.uky.edu/cgi/viewcontent.cgi?article=1135&context=sbcoa_facpub

First-in-Human Studies of MW01-6-189WH, a Brain-Penetrant ...

MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05020535

Study Details | NCT05020535 | Biomarker and Edema ...

This first-in-patient phase 2a pilot study will assess the safety and tolerability of MW01-6-189WH (hereafter called MW189) in patients with Intracerebral ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7541708/

First‐in‐Human Studies of MW01‐6‐189WH, a Brain ...

MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug‐ ...

8.

braininjuryoutcomes.com

braininjuryoutcomes.com/about-the-beach-trial/

About the BEACH Trial

BEACH is a trial studying the safety and tolerability of MW01-6-189WH, a small-molecule drug called MW189, in patients with intracerebral hemorrhage (ICH).

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02942771

A MAD Study of TT301/MW189 in Healthy Volunteers

MW189 has previously been given to healthy human volunteers as a single dose, and there were no significant problems or bad effects in people who received the ...