Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH)

Study Overview
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Brief Summary
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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 Hemorrhage (ICH).

Detailed Description
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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 Hemorrhage (ICH). This study will monitor exploratory radiographic and clinical endpoints, explore the use of biochemical biomarkers to demonstrate target engagement and biological response to a potential new therapy targeted to neuroinflammation and synaptic dysfunction mechanisms. MW189 is a novel small molecule drug candidate developed as a selective suppressor of disease-and injury-induced proinflammatory cytokine overproduction associated with destructive neuroinflammation/synaptic dysfunction cycles. In animal models of acute brain injuries such as ICH and Traumatic Brain Injury (TBI), MW189 attenuates neuroinflammation, reduces cerebral edema, and improves functional and cognitive performance. The investigators seek to establish if these targets are modified in humans with ICH.

Official Title
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Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) Phase 2a Trial

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: MW189
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of spontaneous, non-traumatic ICH. 10 mL ≤ ICH ≤ 60 mL (confirmed via diagnostic and stability CT scans utilizing volumetric assessment) Participants receiving anticoagulants are eligible upon reversal and stability within 24hrs after onset of ICH symptoms Age ≥ 18 years Able to receive first dose of test article ≤ 24h after onset of ICH symptoms NIHSS score ≥ 2 at randomization or Glasgow Coma Scale ≥ 5 at randomization Controlled blood pressure (systolic BP < 180 mm Hg) at randomization. Premorbid magnetic resonance spectroscopy (mRS) of 0-2 Has adequate venous access No planned surgical intervention except EVD Written informed consent from the patient or legally authorized representative (LAR) Exclusion Criteria: Unstable hematoma defined as > 6 mL increase as compared to previous CT volume taken at least 6 hours apart within 24 hrs after onset of ICH symptoms. Anticipated neurosurgical evacuation by open surgery or minimally invasive surgery with or without Alteplase (EVD allowed). Uncontrolled temp >38.5˚C at enrollment. Signs of intracranial infection or emergence of a systemic infection Is pregnant or lactating Signs of liver and kidney chronic disease (i.e. creatinine >2, bilirubin > 3, receiving dialysis) Non-reversible bleeding diathesis Used any chronic immunosuppressants or chronic anti-inflammatory drugs (excluding low-dose aspirin), by any route of administration within the past 7 days. Anticipated withdrawal of life-sustaining therapies within the first week after admission. In the opinion of the investigator, patient has any contraindication to the planned study assessments. 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. Concomitant enrollment in another acute interventional study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel 1:1
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>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) | Drug: MW189<br>* 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)<br>|
| Placebo Comparator: Control<br>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) | Other: Saline<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the proportion of all cause-morality between arms | Assess the safety and tolerability of MW189 for patients as determined by the rate of death during the treatment period. | 7 days post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracerebral hemorrhage, MW01-6-189WH, MW189, Radiographic perihematomal edema, Neuroinflammation, Cerebral edema