Proof-of-Concept Study of a Selective p38 MAPK Alpha Inhibitor, Neflamapimod, in Subjects With Mild Alzheimer's Disease
NCT ID: NCT03402659
Last Updated: 2021-10-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
161 participants
INTERVENTIONAL
2017-12-29
2019-07-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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neflamapimod
40 mg hard gelatin capsules, taken twice daily with food.
neflamapimod
40 mg neflamapimod capsule
placebo
hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food.
placebo
matching placebo capsule
Interventions
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neflamapimod
40 mg neflamapimod capsule
placebo
matching placebo capsule
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Willing and able to provide informed consent.
3. Must have mild cognitive impairment (MCI) or mild AD with evidence of progression ("Mild-AD"), as defined by the following:
1. CDR-Global Score of 0.5 or 1.0, with CDR memory subscore of at least 0.5.
2. MMSE score ranging from 20 to 28, inclusive.
3. Positive biomarker for AD, as defined by a CSF Aβ1-42R below the threshold and phospho-tau above the threshold for the assay utilized in the study and assessed by the central laboratory.
4. Computed tomography (CT) or magnetic resonance imaging (MRI) findings within 2 years of Screening that are compatible with AD and no other pathologic processes that might potentially account for the subject's cognitive impairment.
5. If the subject is taking a single drug for AD (e.g., donepezil or other cholinesterase inhibitors or memantine; dual therapy is excluded), he/she has been on a stable dose for at least 2 months prior to baseline, and the dose must remain unchanged during the study unless required for management of adverse events (AEs).
6. Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
7. Must have reliable informant or caregiver.
Exclusion Criteria
2. Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS), or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
3. History of major and active psychiatric disorder, moderate to severe depressive symptoms, and or other concurrent medical condition that, EIP-VX17-745-304, Version 1.0, 17 November, 2017 Page 7 of 46 EIP Pharma, LLC Confidential in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
4. Diagnosis of alcohol or drug abuse within the previous 2 years.
5. History of cancer within the last 5 years, except basal cell carcinoma, squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
6. Poorly controlled clinically significant medical illness.
7. History of serum B12 abnormality, anemia with hemoglobin ≤10 g/dL, thyroid function abnormality, electrolyte abnormality, or positive syphilis serology that have not been corrected and/or otherwise addressed.
8. History of epilepsy or unexplained seizure within the past 5 years.
9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 × the upper limit of normal (ULN), total bilirubin \>2 × ULN, and/or International Normalized Ratio (INR) \>1.5
10. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
11. Subject participated in a study of an investigational drug less than 3 months or 5 half-lives of the investigation drug, whichever is longer, before enrollment in this study.
55 Years
85 Years
ALL
No
Sponsors
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Worldwide Clinical Trials
OTHER
Amsterdam UMC, location VUmc
OTHER
EIP Pharma Inc
INDUSTRY
Responsible Party
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Principal Investigators
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John Alam, MD
Role: STUDY_DIRECTOR
EIP Pharma
Locations
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Alliance for Research
Long Beach, California, United States
Pacific Research Network
San Diego, California, United States
CITrials
Santa Ana, California, United States
Southern California Research, LLC
Simi Valley, California, United States
Viking Clinical Research
Temecula, California, United States
Miami Dade Medical Research Institute
Miami, Florida, United States
Sensible Healthcare, LLC
Ocoee, Florida, United States
Anchor Neuroscience
Pensacola, Florida, United States
Progressive Medical Research
Port Orange, Florida, United States
Suncoast Neuroscience Associates, Inc.
St. Petersburg, Florida, United States
Florida Premier Research Institute
Winter Park, Florida, United States
Northwest Clinical Trials
Boise, Idaho, United States
MassGeneral Institute for Neurodegenerative Disease
Charlestown, Massachusetts, United States
Manhattan Behavioral Medicine
New York, New York, United States
Alzheimer's Memory Center and Research Institute
Charlotte, North Carolina, United States
Northwest Clinical Research Center
Seattle, Washington, United States
Neuro HK, s.r.o. POLIKLINIKA CHOCEŇ, a.s.
Choceň, , Czechia
Cerebrovaskulární poradna s.r.o.
Moravská Ostrava, , Czechia
Clintrial S.R.O
Prague, , Czechia
Private Psychiatric Centre
Prague, , Czechia
Vestra Clinics S.R.O
Rychnov nad Kněžnou, , Czechia
CCBR Clinical Research, Aalborg
Aalborg, , Denmark
CCBR Clinical Research, Ballerup
Ballerup Municipality, , Denmark
CCBR Clinical Research, Vejle
Vejle, , Denmark
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, , Netherlands
Alzheimer Research Center
Amsterdam, , Netherlands
Amphia Ziekhuis
Breda, , Netherlands
MAC Clinical Research Tankersley
Barnsley, , United Kingdom
Re:Cognition Health Birmingham
Birmingham, , United Kingdom
MAC Clinical Research Blackpool
Blackpool, , United Kingdom
Fulbourn Hospital
Cambridge, , United Kingdom
MAC Clinical Research Leeds
Leeds, , United Kingdom
MAC Clinical Research Liverpool
Liverpool, , United Kingdom
Re:Cognition Health London
London, , United Kingdom
St. Pancras Clinical Research
London, , United Kingdom
MAC Clinical Research Manchester
Manchester, , United Kingdom
Re:Cognition Health Plymouth
Plymouth, , United Kingdom
5 Boroughs/North West Boroughs Healthcare NHS Foundation Trust
Warrington, , United Kingdom
Countries
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References
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Prins ND, Harrison JE, Chu HM, Blackburn K, Alam JJ, Scheltens P; REVERSE-SD Study Investigators. A phase 2 double-blind placebo-controlled 24-week treatment clinical study of the p38 alpha kinase inhibitor neflamapimod in mild Alzheimer's disease. Alzheimers Res Ther. 2021 May 27;13(1):106. doi: 10.1186/s13195-021-00843-2.
Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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EIP-VX17-745-304
Identifier Type: -
Identifier Source: org_study_id