MW150 Stress Kinase Inhibitor in Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This study is a phase 2a randomized double-blind, placebo-controlled, study, in mild-to-moderate Alzheimer's disease, of the oral investigational drug MW150, a p38alphaMAPK kinase inhibitor. The primary goals of this study are to investigate the safety and tolerability, and drug movements in the body. The secondary goals of the study are to investigate the effects of the drug on cognitive performance, activities of daily living, and behavior, and the biological effects of the drug on blood biomarkers.

Official Title
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A Phase 2a Study of MW150 Stress Kinase Inhibitor in Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: MW150
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent from subject (or legally authorized representative, LAR) and study partner. Male or female, age 50 to 90 inclusive. Have a study partner who is able to accompany the subject, has frequent contact with subject. Meet criteria for Alzheimer's Disease by NIAA-AA criteria. Must speak English fluently. Must have education of at least 8 years. Must have adequate hearing and visual abilities. MMSE score of 14 to 28. Clinical Dementia Rating (CDR) Global score of 0.5 to 2.0 inclusive. Absence of suicidal ideation for at least 1 year. Absence of medical conditions that could affect ability to participate in study. MRI within 1 year of screening, not showing clinically significant structural lesions. Subjects without available MRI within 1 year, must have an MRI performed for eligibility. Stable neuropsychiatric medications for at least 2 months prior to screening. If female, must not be of childbearing potential, as defined by being postmenopausal (more than 1 year without periods) or surgically sterile for at least 6 months prior to screening. If male, must agree to use contraception if with a potentially childbearing partner. Exclusion Criteria: Presence of clinically significant disorders of the central nervous system other than Alzheimer's disease, such as Lewy Body Disease, Parkinson's disease, hydrocephalus, epilepsy, demyelinating disease, brain tumors, or psychiatric disorders (such as schizophrenia, or severe affective disorders). Serious or unstable hematologic, hepatic, renal, pulmonary, cardiac, or other medical disease. Abnormal liver function tests (ALT or AST) or creatine kinase (CK) upon repeat testing. Chronic hepatitis B or C infection, indicated by positive HBSAg, or HCV-Ab with HCV RNA presence. Known history of human immunodeficiency virus (HIV) infection. Known immune disorder that has a history of requiring treatment with immunosuppressive drugs within the past 1 year. Have a drug or alcohol abuse within 12 months prior to screening. Clinically significant laboratory abnormalities at screening. Screening ECG showing repeated QTcF > 480 msec, or other clinically significant ECG abnormalities. Clinically significant structural brain abnormalities, such as hydrocephalus or intra-axial brain tumors. Participation in another investigational study within 30 days or 5 half-lives prior to screening, whichever is greater. Participation in another study that would have cognitive testing during the duration of this study. History of Covid19 or other viral infections within 3 months. Have a clinically significant medical, surgical, laboratory, or behavioral abnormality, which in the judgment of the Investigator makes the subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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: double-blind randomized placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10mg MW150 daily<br>10 mg MW150 daily (1 capsule of 10 mg daily) | Drug: MW150<br>* oral-delivered capsule of study drug<br>* Other names: MW01-18-150SRM;|
| Placebo Comparator: placebo daily<br>placebo daily (1 capsule of matched placebo daily) | Drug: Placebo<br>* oral delivered capsule matched to study drug capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Safety- Blood tests | Number of participants with treatment-related adverse events as assessed by laboratory test abnormalities. | 84 days treatment | 
| Drug Safety- Electrocardiographic | Number of participants with emergent abnormal electrocardiograms. | 84 days treatment | 
| Drug Safety- C-SSRS | Development of any suicidality on COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) score (minimum 0, no maximum, higher number worse). | 84 days treatment | 
| Drug Tolerability- Adverse events | Incidence of adverse events (AE). | 84 days treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive change-MMSE | Change in MiniMental State Examination (MMSE) score (0-30, higher score better). | 84 days treatment | 
| Cognitive change-ADAScog | Change in Alzheimer's Disease Assessment Scale (ADAScog) score (0-70, higher score worse). | 84 days treatment | 
| Cognitive change-Executive | Change in Trails A (0 - 150 sec) and Trails B test scores (0-300 sec), higher scores worse. | 84 days treatment | 
| Cognitive change-Language | Change in Verbal Fluency tests for animals and letters (both minimum 0, no maximum, higher scores better). | 84 days treatment | 
| Functional performance- ADCS-ADL | Change in Alzheimers Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale (0 - 78, higher score better). | 84 days treatment | 
| Functional performance-CDR | Change in Clinical Disease Rating Scale (0 - 3, higher score worse). | 84 days treatment | 
| Behavioral Scale - NPI-Q | Change in Neuropsychiatric Inventory Questionnaire (NPI-Q) (0-36, higher scores worse). | 84 days treatment | 
| Pharmacodynamics - cytokines | Changes in biomarker measurements of plasma levels of cytokines (IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-22, and TNFα) by Simoa assay (pg/mL). | 84 days treatment | 
| Pharmacodynamics - neuronal biomarkers | Changes in biomarker measurements of plasma levels of tau protein and NfL protein by Simoa assay (pg/mL). | 84 days treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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p38alphaMAPK; dementia