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CompletedNCT04001517AscenD-LBUpdated Jun 29, 2023Results posted

Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies

A Phase 2 interventional study of Neflamapimod in Dementia With Lewy Bodies (DLB), sponsored by EIP Pharma Inc. Completed at 24 sites in 2 countries. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2023-06-29.

Sponsored by EIP Pharma Inc · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
91
Allocation
Randomized
Ages
55 Years and older
Sex
All
01

Study summary

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. The primary objective is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as a potential biomarker for DLB.

02

Conditions studied

  • Dementia With Lewy Bodies (DLB)
03

Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
91 participants (actual)

Study arms

  • Experimental
    Neflamapimod

    40 mg capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing \<80 kg or the TID regimen if weighing ≥80 kg

    Drug: Neflamapimod

  • Placebo comparator
    Placebo

    40 mg matching placebo capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing \<80 kg or the TID regimen if weighing ≥80 kg

    Drug: Neflamapimod

Interventions

  • DrugNeflamapimod

    Double-Blind, Placebo-Controlled

05

What researchers measure

Primary outcomes

  1. Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test

    Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.

    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.

Secondary outcomes

  1. Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)

    Change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score from Baseline to Week 8 and Week 16 based on semi-quantitative scoring of six domains (i.e., "box": 1) memory, 2) orientation, 3) judgement \& reasoning, 4) home \& hobbies, 5) community affairs, and 6) personal care. The CDR score ranges from 0 (no impairment), 0.5 (questionable impairment), 1 (mild impairment), 2 (moderate impairment), and 3 (severe impairment). The domain (box) scores are then added for a Sum of Boxes score. With six domains, the CDR-SB score then ranges from 0 to 18; with higher scores indicated worse outcomes.

    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.

  2. Mini-Mental State Examination (MMSE)

    The Mini-Mental State Examination (MMSE) is a general measure of cognition that assesses orientation, memory, concentration, language, and praxis. Scores range from 0 to 30 with lower scores indicating greater cognitive impairment, i.e. a worse outcome). The MMSE was assessed at Week 8 and Week 16 during the study.

    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.

  3. Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score

    The NPI-10 consists evaluates ten domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor activity. If caregiver reports symptoms within a domain then the caregiver rates the frequency of the symptoms on a 4-point scale, and severity on a 3-point scale. Total score for each domain is the frequency score multiplied by the severity score; i.e. the domain score (e.g. for hallucinations) for any one domain ranges from 0-12, with higher scores indicating worsening. A secondary objective of this study was to evaluate the effect of neflamapimod in four specific domains, specifically depression (dysphoria), anxiety, hallucinations, and agitation/aggression, in neflamapimod-treated subjects compared to placebo-recipients. Of these four, the only domain in which more than one-quarter of the patients reported symptoms is hallucinations, and the result of this analysis is reported.

    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.

  4. International Shopping List Test (ISLT) - Immediate Recall

    The International Shopping List Test (ISLT) was developed specifically to assess verbal list learning and memory in people from different language and cultural backgrounds. 12 words, consisting to items typically in a grocery shopping list in the specific culture are provided verbally, and subject asked to recall ask many words as possible. The immediate recall score consists of the number of words that the subject correctly repeats during three consecutive trials immediately following provision of words. The range is then from 0 to 36 (12 words maximum in each of 3 trials), with higher scores (i.e., the more words recalled) reflecting better outcomes.

    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.

  5. Timed Up and Go Test (TUG)

    The Timed Up and Go test assesses function mobility, and was included in the study to evaluate the effects of neflamapimod on motor function. The TUG measures the time in seconds that a person takes to rise from a chair, walk three meters, turn around 180 degrees, walk back to the chair, and sit down while turning 180 degrees. The TUG was evaluated at Baseline, and Weeks 8 and 16 of the study. There is no minimum or maximum value for this test, though in Parkinson's disease patients values above 11.5 seconds was associated with an increased risk of falls and each one second increase in the time required to complete the TUG is associated with a 5.4% increase in the risk of falls (Arch Phys Med Rehabil. 2013;94: 1300-1305). That is, an increase in the time required to complete the TUG is a worse outcome.

    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.

  6. Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe

    Change in quantitative electroencephalogram (qEEG) parameters with the subject awake in accordance with the 10-20 International System of Electrode placement was to be evaluated as a potential biomarker for DLB. However, due to COVID19 related restrictions, baseline and week 16 EEG recordings were obtained only in limited number of subjects. As slowing of the dominant frequency band by qEEG over posterior aspects of the brain has been recognized to be prominent in DLB, the change in the dominant frequency band over the parietal lobe in Hz from baseline to week 16 is reported. This is a continuous variable with no minimum or maximum. A decrease in the frequency (i.e., slowing) reflects worsening of disease, while a positive treatment effect would be an increase in the frequency. With the limited number of subjects formal statistical analysis was not conducted.

    Time frame: 16 weeks

06

Results

Posted Nov 2, 2021

Participant flow

Participant flow — Overall Study
MilestoneNeflamapimod TIDNeflamapimod BIDPlacebo TIDPlacebo BID
Started20262718
Completed20202615
Not completed0613

Outcome measures

PrimaryComposite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test

Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.

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.
Reported as:
Mean · Z-Score
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test
Z-ScoreNeflamapimod TIDNeflamapimod BIDPlacebo
Baseline0.06 ± 0.170.02 ± 0.150.05 ± 0.11
Week 40.17 ± 0.14-0.08 ± 0.18-0.05 ± 0.13
Week 80.28 ± 0.16-0.12 ± 0.180.05 ± 0.17
Week 160.21 ± 0.18-0.08 ± 0.21-0.03 ± 0.14
Statistical analysis
  • Neflamapimod TID vs Placebo · Mixed Models Analysis · p = 0.049 (The comparison is of neflamapimod 40mg TID to placebo. The p-value was not adjusted for multiple comparisons.) · Mean difference (net): 0.175 · 95% CI 0.001 to 0.345The comparison is of neflamapimod 40mg TID to placebo. The positive value represents a better outcome with neflamapimod 40mg treatment vs. placebo.
  • Neflamapimod TID vs Neflamapimod BID vs Placebo · Mixed Models Analysis · p = >0.2
SecondaryClinical Dementia Rating Scale-Sum of Boxes (CDR-SB)

Change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score from Baseline to Week 8 and Week 16 based on semi-quantitative scoring of six domains (i.e., "box": 1) memory, 2) orientation, 3) judgement \& reasoning, 4) home \& hobbies, 5) community affairs, and 6) personal care. The CDR score ranges from 0 (no impairment), 0.5 (questionable impairment), 1 (mild impairment), 2 (moderate impairment), and 3 (severe impairment). The domain (box) scores are then added for a Sum of Boxes score. With six domains, the CDR-SB score then ranges from 0 to 18; with higher scores indicated worse outcomes.

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.
Reported as:
Mean · Scores on a scale
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
Scores on a scaleNeflamapimod TIDNeflamapimod BIDPlacebo
Week 80.11 ± 0.20.19 ± 0.30.76 ± 0.25
Week 160.34 ± 0.20.34 ± 0.180.86 ± 0.32
Statistical analysis
  • Neflamapimod TID vs Placebo · Mixed Models Analysis · p = 0.007 (Comparison of combined neflamapimod dose groups vs. placebo utilizing mixed model for repeated measures with baseline as a covariate. The p-value is not adjusted for multiple comparisons.) · Mean difference (net): -0.56 · 95% CI -0.96 to -0.16The comparison is of neflamapimod 40mg TID to placebo. A negative value indicates improvement compared to placebo.
  • Neflamapimod TID vs Neflamapimod BID vs Placebo · Mixed Models Analysis · p = 0.023 (Mixed model for repeated measures with baseline as a covariate. The p-value was not adjusted for multiple comparisons) · Mean difference (net): -0.45 · 95% CI -0.83 to -0.06Comparison of combined neflamapimod dose groups vs. placebo. Negative values represents a better outcome with neflamapimod relative to placebo.
SecondaryMini-Mental State Examination (MMSE)

The Mini-Mental State Examination (MMSE) is a general measure of cognition that assesses orientation, memory, concentration, language, and praxis. Scores range from 0 to 30 with lower scores indicating greater cognitive impairment, i.e. a worse outcome). The MMSE was assessed at Week 8 and Week 16 during the study.

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.
Reported as:
Mean · Scores on a scale
Mini-Mental State Examination (MMSE)
Scores on a scaleNeflamapimod TIDNeflamapimod BIDPlacebo
Week 80.11 ± 0.740.08 ± 0.64-0.59 ± 0.38
Week 16-0.85 ± .49-1.75 ± 0.67-0.53 ± 0.49
Statistical analysis
  • Neflamapimod TID vs Neflamapimod BID vs Placebo · Mixed Models Analysis · p = >0.2
SecondaryNeuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score

The NPI-10 consists evaluates ten domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor activity. If caregiver reports symptoms within a domain then the caregiver rates the frequency of the symptoms on a 4-point scale, and severity on a 3-point scale. Total score for each domain is the frequency score multiplied by the severity score; i.e. the domain score (e.g. for hallucinations) for any one domain ranges from 0-12, with higher scores indicating worsening. A secondary objective of this study was to evaluate the effect of neflamapimod in four specific domains, specifically depression (dysphoria), anxiety, hallucinations, and agitation/aggression, in neflamapimod-treated subjects compared to placebo-recipients. Of these four, the only domain in which more than one-quarter of the patients reported symptoms is hallucinations, and the result of this analysis is reported.

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.
Reported as:
Mean · Score on a scale
Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score
Score on a scaleNeflamapimod 40 mg BIDNeflamapimod TIDPlacebo
Week 40.1 ± .875-1.71 ± 1.230.56 ± 0.697
Week 80.63 ± .46-0.86 ± 1.220.86 ± 0.61
Week 163.29 ± 1.97-0.5 ± 1.21.71 ± 1.19
Statistical analysis
  • Neflamapimod TID vs Placebo · Mixed Models Analysis · p = 0.15 · Mean difference (net): -1.53 · 95% CI -3.61 to .55
  • Neflamapimod 40 mg BID vs Neflamapimod TID vs Placebo · Mixed Models Analysis · p = 0.077 · Mean difference (net): -1.31 · 95% CI -5.03 to 2.34
SecondaryInternational Shopping List Test (ISLT) - Immediate Recall

The International Shopping List Test (ISLT) was developed specifically to assess verbal list learning and memory in people from different language and cultural backgrounds. 12 words, consisting to items typically in a grocery shopping list in the specific culture are provided verbally, and subject asked to recall ask many words as possible. The immediate recall score consists of the number of words that the subject correctly repeats during three consecutive trials immediately following provision of words. The range is then from 0 to 36 (12 words maximum in each of 3 trials), with higher scores (i.e., the more words recalled) reflecting better outcomes.

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.
Reported as:
Mean · Scores on a scale
International Shopping List Test (ISLT) - Immediate Recall
Scores on a scaleNeflamapimod TIDNeflamapimod BIDPlacebo
Change from baseline to week 40.29 ± 1.08-1.24 ± 0.610.11 ± 0.54
Change from baseline to week 82.11 ± 1.66-0.75 ± 1.370.41 ± 0.65
Change from baseline to week 160.30 ± 1.040.11 ± .99-0.15 ± .46
Statistical analysis
  • Neflamapimod TID vs Neflamapimod BID vs Placebo · Mixed Models Analysis · p = >0.2 · Mean difference (net): 0.32 · 95% CI -1.27 to 1.91Comparison of change from baseline over course of study for NFMD 40mg TID vs. placebo.
SecondaryTimed Up and Go Test (TUG)

The Timed Up and Go test assesses function mobility, and was included in the study to evaluate the effects of neflamapimod on motor function. The TUG measures the time in seconds that a person takes to rise from a chair, walk three meters, turn around 180 degrees, walk back to the chair, and sit down while turning 180 degrees. The TUG was evaluated at Baseline, and Weeks 8 and 16 of the study. There is no minimum or maximum value for this test, though in Parkinson's disease patients values above 11.5 seconds was associated with an increased risk of falls and each one second increase in the time required to complete the TUG is associated with a 5.4% increase in the risk of falls (Arch Phys Med Rehabil. 2013;94: 1300-1305). That is, an increase in the time required to complete the TUG is a worse outcome.

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.
Reported as:
Mean · Seconds
Timed Up and Go Test (TUG)
SecondsNeflamapimod TIDNeflamapimod BIDPlacebo
Week 8-0.2 ± 0.51.0 ± 0.90.4 ± 0.4
Week 16-1.4 ± 1.01.3 ± 0.71.5 ± 0.9
Statistical analysis
  • Neflamapimod TID vs Placebo · Mixed Models Analysis · p = 0.024 · Mean difference (net): -1.4 · 95% CI -2.6 to -0.2Mean difference for the comparison of 40 mg TID vs. placebo is reported.
  • Neflamapimod TID vs Neflamapimod BID vs Placebo · Mixed Models Analysis · p = 0.044 · Mean difference (net): -1.36 · 95% CI -2.69 to -0.04
SecondaryQuantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe

Change in quantitative electroencephalogram (qEEG) parameters with the subject awake in accordance with the 10-20 International System of Electrode placement was to be evaluated as a potential biomarker for DLB. However, due to COVID19 related restrictions, baseline and week 16 EEG recordings were obtained only in limited number of subjects. As slowing of the dominant frequency band by qEEG over posterior aspects of the brain has been recognized to be prominent in DLB, the change in the dominant frequency band over the parietal lobe in Hz from baseline to week 16 is reported. This is a continuous variable with no minimum or maximum. A decrease in the frequency (i.e., slowing) reflects worsening of disease, while a positive treatment effect would be an increase in the frequency. With the limited number of subjects formal statistical analysis was not conducted.

Time frame:
16 weeks
Reported as:
Mean · Hz
Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe
HzNeflamapimod TIDPlacebo
Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe0.24 ± 1.060.36 ± 0.95

Adverse events

Collected over AEs occurring from when the subject signed the ICF until the last study event were collected. (Study Duration = 16 weeks) Any AEs occurring before the start of treatment (i.e., before the first dose of the investigational product) were recorded in the medical history.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Neflamapimod TID0/20 (0%)0/20 (0%)8/20 (40%)
Neflamapimod BID0/26 (0%)3/26 (11.5%)8/26 (30.8%)
Placebo2/45 (4.4%)4/45 (8.9%)17/45 (37.8%)
Most frequent serious events
Most frequent serious events
EventNeflamapimod TIDNeflamapimod BIDPlacebo
New brain lesions of unclear etiologyNervous system disorders0/201/260/45
Diagnosis of brain tumorNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/201/260/45
Head injuryInjury, poisoning and procedural complications0/201/260/45
HematocheziaGastrointestinal disorders0/200/261/45
Asthma exacerbationRespiratory, thoracic and mediastinal disorders0/200/261/45
Intraparenchymal hemorrhageNervous system disorders0/200/261/45
Internal bleedingBlood and lymphatic system disorders0/200/261/45
Most frequent other events
Most frequent other events
EventNeflamapimod TIDNeflamapimod BIDPlacebo
FallInjury, poisoning and procedural complications1/205/264/45
DiarrheaGastrointestinal disorders3/200/265/45
HeadacheNervous system disorders3/201/262/45
NauseaGastrointestinal disorders1/202/263/45
TremorNervous system disorders0/200/263/45

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
<=18 years0000
Between 18 and 65 years22711
>=65 years18243880
Age, Continuous
Age, Continuous(years)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
Mean72.2 (59 to 84)74.5 (63 to 85)72.1 (62 to 87)72.8 (59 to 87)
Sex: Female, Male
Sex: Female, Male(Participants)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
Female17614
Male19193977
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
Hispanic or Latino0437
Not Hispanic or Latino20224284
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
American Indian or Alaska Native0000
Asian0000
Native Hawaiian or Other Pacific Islander0000
Black or African American0011
White20264490
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Neflamapimod TIDNeflamapimod BIDPlaceboTotal
Netherlands34613
United States17223978
MMSE
MMSE(units on a scale (range 0-30))Neflamapimod TIDNeflamapimod BIDPlaceboTotal
Mean23.6 ± 3.722.4 ± 3.723.0 ± 4.123.0 ± 3.5
07

Study locations

24 sites
  • University of California San Diego (UCSD)
    La Jolla, California 92037, United States
  • Pacific Neuroscience Institute
    Santa Monica, California 90404, United States
  • University of Colorado
    Aurora, Colorado 80045, United States
  • Elite Clinical Research
    Miami, Florida 33144, United States
  • University of Kansas Medical Center
    Kansas City, Kansas 66103, United States
  • Massachusetts General Hospital
    Charlestown, Massachusetts 02129, United States
  • University of Michigan
    Ann Arbor, Michigan 48105, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Cleveland Clinic - Lou Ruvo Center for Brain Health
    Las Vegas, Nevada 89106, United States
  • New York Presbyterian Hospital - Columbia University Medical Center
    New York, New York 10032, United States
  • University of Rochester
    Rochester, New York 14618, United States
  • University of North Carolina
    Chapel Hill, North Carolina 27599, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • The Ohio State University
    Columbus, Ohio 43210, United States
  • Summit Research Network
    Portland, Oregon 97210, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
  • University of Virginia
    Charlottesville, Virginia 22908, United States
  • National Clinical Research, Inc.
    Richmond, Virginia 23294, United States
  • Northwest Clinical Research Center
    Bellevue, Washington 98007, United States
  • University of Washington
    Seattle, Washington 98104, United States
  • Inland Northwest Research
    Spokane, Washington 99202, United States
  • Brain Research Center
    Amsterdam, Netherlands
  • Brain Research Center
    Den Bosch, Netherlands
08

References and documents

Publications

  • Jiang Y, Alam JJ, Gomperts SN, Maruff P, Lemstra AW, Germann UA, Stavrides PH, Darji S, Malampati S, Peddy J, Bleiwas C, Pawlik M, Pensalfini A, Yang DS, Subbanna S, Basavarajappa BS, Smiley JF, Gardner A, Blackburn K, Chu HM, Prins ND, Teunissen CE, Harrison JE, Scheltens P, Nixon RA. Preclinical and randomized clinical evaluation of the p38alpha kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration. Nat Commun. 2022 Sep 21;13(1):5308. doi: 10.1038/s41467-022-32944-3. PubMed 36130946 ↗

Study documents

  • Study protocol · Apr 12, 2019
  • Statistical analysis plan · Jun 30, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04001517
Lead sponsor
EIP Pharma Inc
Collaborators
Worldwide Clinical Trials
Responsible party
Sponsor
First posted
Jun 28, 2019
Start date
Sep 30, 2019
Primary completion
Jun 30, 2020
Completion
Jun 30, 2020
Results posted
Nov 2, 2021
Last update
Jun 29, 2023

Study contacts

John Alam, MD
study director · EIP Pharma

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.

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EIP Pharma Inc

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