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AscenD-LB
CompletedPhase 2Results postedCognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies
A Double-Blind, Placebo-Controlled 16-Week Study of the Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (DLB)
Lead sponsor
Asset
Neflamapimod
Listed sites
24
Recruiting sites
-
Enrollment
91
actual
Study population
Lewy body dementia
Key I/E criteria
•Dementia with Lewy bodies•MMSE 15-28•Study partner/caregiver required•AD symptomatic therapy: stable ≥6 weeks
Primary endpoint
•Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB)
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
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Men and women aged ≥55 years.
2. Subject or subject's legally authorized representative is willing and able to provide written informed consent.
3. Probable DLB and identified cognitive deficits, according to current consensus criteria (McKeith et al, 2017), specifically one core clinical feature and a positive DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the subject would also qualify.
4. MMSE score of 15-28, inclusive, during Screening.
5. Currently receiving cholinesterase inhibitor therapy, having received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
6. Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
7. No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
8. Must have reliable informant or caregiver
Exclusion criteria
1. Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB, including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's disease (AD), or Parkinson's disease (PD).
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 C-SSRS, or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
3. Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, 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. Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would interfere with assessment of drug safety.
6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5.
7. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
8. Participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
9. History of previous neurosurgery to the brain.
10. If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
11. If female who has not has not reached menopause >1 year previously or has not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.
Endpoints (14)
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
Global cognition
6 endpointsComposite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test
Time frame:As the analysis was by Mixed Model for Repeated Measures, all time points at which NTB was assessed utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
change from baseline, improvement
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test
Time frame:As the analysis was by Mixed Model for Repeated Measures, all time points at which NTB was assessed utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
change from baseline, improvement
Posted result
| Group | Value (mean), Z-Score | Standard error |
|---|---|---|
| Neflamapimod TIDBaselinen=19 Participants | 0.06 | 0.17 |
| Week 4n=19 Participants | 0.17 | 0.14 |
| Week 8n=19 Participants | 0.28 | 0.16 |
| Week 16n=19 Participants | 0.21 | 0.18 |
| Neflamapimod BIDBaselinen=20 Participants | 0.02 | 0.15 |
| Week 4n=20 Participants | -0.08 | 0.18 |
| Week 8n=20 Participants | -0.12 | 0.18 |
| Week 16n=20 Participants | -0.08 | 0.21 |
| PlaceboBaselinen=37 Participants | 0.05 | 0.11 |
| Week 4n=37 Participants | -0.05 | 0.13 |
| Week 8n=37 Participants | 0.05 | 0.17 |
| Week 16n=37 Participants | -0.03 | 0.14 |
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which CDR-SB was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Mini-Mental State Examination (MMSE)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which MMSE was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Mini-Mental State Examination (MMSE)
concentration, descriptive
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which CDR-SB was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Posted result
| Group | Value (mean), Scores on a scale | Standard error |
|---|---|---|
| Neflamapimod TIDWeek 8n=20 Participants | 0.11 | 0.2 |
| Week 16n=20 Participants | 0.34 | 0.2 |
| Neflamapimod BIDWeek 8n=20 Participants | 0.19 | 0.3 |
| Week 16n=20 Participants | 0.34 | 0.18 |
| PlaceboWeek 8n=37 Participants | 0.76 | 0.25 |
| Week 16n=37 Participants | 0.86 | 0.32 |
A secondary analysis was conducted comparing the combined neflamapimod dose groups vs. placebo.
Mini-Mental State Examination (MMSE)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which MMSE was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Mini-Mental State Examination (MMSE)
concentration, descriptive
Posted result
| Group | Value (mean), Scores on a scale | Standard error |
|---|---|---|
| Neflamapimod TIDWeek 8n=20 Participants | 0.11 | 0.74 |
| Week 16n=20 Participants | -0.85 | .49 |
| Neflamapimod BIDWeek 8n=21 Participants | 0.08 | 0.64 |
| Week 16n=21 Participants | -1.75 | 0.67 |
| PlaceboWeek 8n=37 Participants | -0.59 | 0.38 |
| Week 16n=37 Participants | -0.53 | 0.49 |
Memory
2 endpointsInternational Shopping List Test (ISLT) - Immediate Recall
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which ISLT was assessed (Weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
event count, event
International Shopping List Test (ISLT) - Immediate Recall
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which ISLT was assessed (Weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
event count, event
Posted result
| Group | Value (mean), Scores on a scale | Standard error |
|---|---|---|
| Neflamapimod TIDChange from baseline to week 4n=17 Participants | 0.29 | 1.08 |
| Change from baseline to week 8n=9 Participants | 2.11 | 1.66 |
| Change from baseline to week 16n=20 Participants | 0.30 | 1.04 |
| Neflamapimod BIDChange from baseline to week 4n=20 Participants | -1.24 | 0.61 |
| Change from baseline to week 8n=12 Participants | -0.75 | 1.37 |
| Change from baseline to week 16n=20 Participants | 0.11 | .99 |
| PlaceboChange from baseline to week 4n=41 Participants | 0.11 | 0.54 |
| Change from baseline to week 8n=29 Participants | 0.41 | 0.65 |
| Change from baseline to week 16n=41 Participants | -0.15 | .46 |
Behavior / neuropsychiatric
2 endpointsNeuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score
Time frame:As the analysis was by Mixed Model for Repeated Measures, all time points at which NPI-10 was assessed (weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Neuropsychiatric Inventory (NPI)
change from baseline, improvement
Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score
Time frame:As the analysis was by Mixed Model for Repeated Measures, all time points at which NPI-10 was assessed (weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
Neuropsychiatric Inventory (NPI)
change from baseline, improvement
Posted result
| Group | Value (mean), Score on a scale | Standard error |
|---|---|---|
| Neflamapimod 40 mg BIDWeek 4n=9 Participants | 0.1 | .875 |
| Week 8n=9 Participants | 0.63 | .46 |
| Week 16n=9 Participants | 3.29 | 1.97 |
| Neflamapimod TIDWeek 4n=8 Participants | -1.71 | 1.23 |
| Week 8n=8 Participants | -0.86 | 1.22 |
| Week 16n=8 Participants | -0.5 | 1.2 |
| PlaceboWeek 4n=10 Participants | 0.56 | 0.697 |
| Week 8n=10 Participants | 0.86 | 0.61 |
| Week 16n=10 Participants | 1.71 | 1.19 |
Comparison of combined neflamapimod groups (i.e., all neflamapimod) vs. placebo
Fluid / digital biomarkers
2 endpointsQuantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe
Time frame:16 weeks
change from baseline, improvement
Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe
Time frame:16 weeks
change from baseline, improvement
Posted result
| Group | Value (mean), Hz | Standard deviation |
|---|---|---|
| Neflamapimod TIDn=6 Participants | 0.24 | 1.06 |
| Placebon=12 Participants | 0.36 | 0.95 |
Other clinical outcomes
2 endpointsTimed Up and Go Test (TUG)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which the TUG was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
descriptive
Timed Up and Go Test (TUG)
Time frame:As the analysis was by Mixed Model for Repeated Measures, both time points at which the TUG was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.
descriptive
Posted result
| Group | Value (mean), Seconds | Standard error |
|---|---|---|
| Neflamapimod TIDWeek 8n=20 Participants | -0.2 | 0.5 |
| Week 16n=20 Participants | -1.4 | 1.0 |
| Neflamapimod BIDWeek 8n=20 Participants | 1.0 | 0.9 |
| Week 16n=20 Participants | 1.3 | 0.7 |
| PlaceboWeek 8n=37 Participants | 0.4 | 0.4 |
| Week 16n=37 Participants | 1.5 | 0.9 |
Publications (2)
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
- PMID36130946via DERIVED
- PMID37657939via DERIVED
Provenance
Sources
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.