MW150 Stress Kinase Inhibitor in Mild to Moderate Alzheimer's Disease (SKI-AD)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: MW150; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lawrence S Honig, MD PhD; Phone Number: 2123059194; Email: lh456@cumc.columbia.edu
• Study Contact Backup: Name: Wayne P Anderson, PhD; Email: nkt.wanderson@gmail.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
      • Contact: Lawrence S Honig, MD PhD; Phone Number: 212-305-9194; Email: lh456@cumc.columbia.edu
      • Contact: Katrina Cuasay, AB; Phone Number: 2123052077; Email: kc2305@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent from subject (or legally authorized representative, LAR) and study partner.
2. Male or female, age 50 to 90 inclusive.
3. Have a study partner who is able to accompany the subject, has frequent contact with subject.
4. Meet criteria for Alzheimer's Disease by NIAA-AA criteria.
5. Must speak English fluently.
6. Must have education of at least 8 years.
7. Must have adequate hearing and visual abilities.
8. MMSE score of 14 to 28.
9. Clinical Dementia Rating (CDR) Global score of 0.5 to 2.0 inclusive.
10. Absence of suicidal ideation for at least 1 year.
11. Absence of medical conditions that could affect ability to participate in study.
12. 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.
13. Stable neuropsychiatric medications for at least 2 months prior to screening.
14. 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.
15. If male, must agree to use contraception if with a potentially childbearing partner.

Exclusion Criteria:

1. 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).
2. Serious or unstable hematologic, hepatic, renal, pulmonary, cardiac, or other medical disease.
3. Abnormal liver function tests (ALT or AST) or creatine kinase (CK) upon repeat testing.
4. Chronic hepatitis B or C infection, indicated by positive HBSAg, or HCV-Ab with HCV RNA presence.
5. Known history of human immunodeficiency virus (HIV) infection.
6. Known immune disorder that has a history of requiring treatment with immunosuppressive drugs within the past 1 year.
7. Have a drug or alcohol abuse within 12 months prior to screening.
8. Clinically significant laboratory abnormalities at screening.
9. Screening ECG showing repeated QTcF > 480 msec, or other clinically significant ECG abnormalities.
10. Clinically significant structural brain abnormalities, such as hydrocephalus or intra-axial brain tumors.
11. Participation in another investigational study within 30 days or 5 half-lives prior to screening, whichever is greater.
12. Participation in another study that would have cognitive testing during the duration of this study.
13. History of Covid19 or other viral infections within 3 months.
14. Have a clinically significant medical, surgical, laboratory, or behavioral abnormality, which in the judgment of the Investigator makes the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neurokine Therapeutics
• Collaborators: Columbia University; National Institute on Aging (NIA)
• Investigators: Principal Investigator: Lawrence S Honig, MD PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): November 30, 2024

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 13, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: p38alphaMAPK; dementia
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: MW150-AD-201; R44AG071388 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Once study complete, de-identified participant data will be shared upon request by investigators from an academic institution.
• IPD Sharing Time Frame: ICF will be shared at onset of enrollment. Study Protocol and SAP will be shared once study published. CSR will be shared once completed.
• IPD Sharing Access Criteria: Protocol, SAP will be shared via publication. CSR will be shared upon request
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No