CompletedPhase 2Results posted

Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD

A Randomized, Open-Label, Multiple Dose Clinical Pharmacology Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745 in Patients With Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) or With Mild AD

Lead sponsor

EIP Pharma Inc

Asset

Neflamapimod

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•MCI due to AD•MMSE 20-30

Primary endpoint

•Cerebrospinal Fluid Levels of Cytokines

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDEIP14-745-303

NCT IDNCT02423200

Timeline

Milestones

Study start2015-04 (month precision)

Study first posted2015-04-22estimated

Primary completion2016-09actual (month precision)

Study completion2016-11actual (month precision)

Last update posted2018-04-03actual

Results first posted2018-04-03actual

Assets

Drug assets

Neflamapimod

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age60 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age 60 - 85 (inclusive)

•Willing and able to provide informed consent

•Clinical presentation consistent with MCI due to AD or of mild AD

-Gradual progressive decline in memory function over >6 months

-Amnestic presentation on neuropsychological testing with rapid forgetting (% reduction 1.5 standard deviations below the mean)

-Clinical Dementia Rating (CDR) Sum of Box (SOB) score ≥0.5

-Mini-Mental State Examination (MMSE) range: 20 to 30

•Brain hypometabolism by 18F-2-fluoro-2-deoxyglucose (FDG)-PET

•Participants may be taking medications for AD, provided that the dose of these medications has been stable for >3 months

Exclusion criteria

•Evidence of neurodegenerative disease other than AD

•Inability for any reason to undergo MRI scans (e.g. pacemaker, vascular stent or stent graft). Patients who require sedation for screening procedures such as MRI may receive a short-acting sedative.

•Psychiatric disorder that would compromise ability to comply with study requirements

•History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years

•Significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder or metabolic/endocrine disorders or other disease that would preclude treatment with p38 MAP kinase inhibitor and/or assessment of drug safety and efficacy

•Recent (<90 days) changes to AD medications prescribed for cognitive reasons or with the potential to impact cognition

•Psychotropic drugs taken within 1 month. Anticoagulant drugs taken within 1 week.

•Participation in a study of an investigational drug less than 6 months or 5 half-lives of the investigational drug, whichever is longer, before enrollment in the study

•Male subjects with female partner of child-bearing potential who are unwilling or unable to adhere to contraception requirements

•Female subjects who have not reached menopause or have not had a hysterectomy or bilateral oophorectomy/salpingoophorectomy

•Positive urine or serum pregnancy test or plans desires to become pregnant during the course of the trial

•Donation of >500 mL of blood or blood products within 2 months

•History of alcohol and/or illicit drug abuse within 6 months.

•Infection with hepatitis A, B or C or HIV.

•Any factor deemed by the investigator to be likely to interfere with study conduction

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Fluid / digital biomarkers

Global cognition

Safety / tolerability / PK

Global cognition

2 endpoints

Secondary/protocol endpoint

Episodic Memory Function

Time frame:Change from baseline to Day 42

change from baseline, improvement

Secondary/registry result

Episodic Memory Function

Time frame:Change from baseline to Day 42

change from baseline, improvement

Posted result

Group	Value (mean), points on HLVT Total Recall (range 0-36)	Standard deviation
Overall Study Populationn=8 Participants	3.5	3.6

Fluid / digital biomarkers

4 endpoints

Primary/protocol endpoint

Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines

Time frame:Baseline and Day 42 of dosing with VX-745

percent change from baseline, improvement

Primary/registry result

Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines

Time frame:Baseline and Day 42 of dosing with VX-745

percent change from baseline, improvement

Posted result

Group	Value (mean), percentage of baseline at Day 42	Standard deviation
Overall Study Populationn=7 Participants	137	115

Secondary/protocol endpoint

Maximal CSF VX-745 Concentration

Time frame:All samples with quantifiable CSF drug levels were included (n=12). Eight were obtained 3-hours post-dose, either on Day 1 (n=4) or Day 42 (n=4). 3 samples were at 6-hours post-dose on Day 42; and one was at 6-hours post-dose on Day 1.

concentration, descriptive

Secondary/registry result

Maximal CSF VX-745 Concentration

concentration, descriptive

Posted result

Group	Value (mean), ratio of plasma drug concentration	Standard deviation
Overall Study Populationn=9 Participants	0.062	0.01

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Severe or Serious Adverse Events

Time frame:At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing

event count, event

Secondary/registry result

Severe or Serious Adverse Events

Time frame:At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Neflamapimod (VX-745) Dose Level 1n=8 Participants	0	-
Neflamapimod (VX-745) Dose Level 2n=1 Participants	0	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID33974419via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.