Trial Outcomes & Findings for Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (NCT NCT04001517)

Last Updated: 2023-06-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

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.

Results posted on

2023-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	Neflamapimod TID 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo TID 40 mg matching placebo capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Placebo BID 40 mg matching placebo capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg
Overall Study STARTED	20	26	27	18
Overall Study COMPLETED	20	20	26	15
Overall Study NOT COMPLETED	0	6	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neflamapimod TID n=20 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=26 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=45 Participants Placebo capsules matched to neflamapimod capsules, administered orally BID or TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg or the BID regiment if Screening weight was \<80 kg	Total n=91 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	11 Participants n=4 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	24 Participants n=7 Participants	38 Participants n=5 Participants	80 Participants n=4 Participants
Age, Continuous	72.2 years n=5 Participants	74.5 years n=7 Participants	72.1 years n=5 Participants	72.8 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants	77 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants	84 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	26 Participants n=7 Participants	44 Participants n=5 Participants	90 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Netherlands	3 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants
Region of Enrollment United States	17 participants n=5 Participants	22 participants n=7 Participants	39 participants n=5 Participants	78 participants n=4 Participants
MMSE	23.6 units on a scale (range 0-30) STANDARD_DEVIATION 3.7 • n=5 Participants	22.4 units on a scale (range 0-30) STANDARD_DEVIATION 3.7 • n=7 Participants	23.0 units on a scale (range 0-30) STANDARD_DEVIATION 4.1 • n=5 Participants	23.0 units on a scale (range 0-30) STANDARD_DEVIATION 3.5 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Population: All subjects with a baseline and at least one on-treatment NTB evaluation. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=19 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=20 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=37 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test Baseline	0.06 Z-Score Standard Error 0.17	0.02 Z-Score Standard Error 0.15	0.05 Z-Score Standard Error 0.11
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test Week 4	0.17 Z-Score Standard Error 0.14	-0.08 Z-Score Standard Error 0.18	-0.05 Z-Score Standard Error 0.13
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test Week 8	0.28 Z-Score Standard Error 0.16	-0.12 Z-Score Standard Error 0.18	0.05 Z-Score Standard Error 0.17
Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test Week 16	0.21 Z-Score Standard Error 0.18	-0.08 Z-Score Standard Error 0.21	-0.03 Z-Score Standard Error 0.14

SECONDARY outcome

Timeframe: 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.

Population: All subjects with a baseline and at least one on-treatment CDR-SB evaluation. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=20 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=20 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=37 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Week 8	0.11 Scores on a scale Standard Error 0.2	0.19 Scores on a scale Standard Error 0.3	0.76 Scores on a scale Standard Error 0.25
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Week 16	0.34 Scores on a scale Standard Error 0.2	0.34 Scores on a scale Standard Error 0.18	0.86 Scores on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: 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.

Population: All subjects with a baseline and at least one on-treatment MMSE evaluation. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=20 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=21 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=37 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Mini-Mental State Examination (MMSE) Week 8	0.11 Scores on a scale Standard Error 0.74	0.08 Scores on a scale Standard Error 0.64	-0.59 Scores on a scale Standard Error 0.38
Mini-Mental State Examination (MMSE) Week 16	-0.85 Scores on a scale Standard Error .49	-1.75 Scores on a scale Standard Error 0.67	-0.53 Scores on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: 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.

Population: All subjects with a baseline and at least one on-treatment NPI-10 evaluation. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=9 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=8 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=10 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score Week 4	0.1 Score on a scale Standard Error .875	-1.71 Score on a scale Standard Error 1.23	0.56 Score on a scale Standard Error 0.697
Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score Week 8	0.63 Score on a scale Standard Error .46	-0.86 Score on a scale Standard Error 1.22	0.86 Score on a scale Standard Error 0.61
Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score Week 16	3.29 Score on a scale Standard Error 1.97	-0.5 Score on a scale Standard Error 1.2	1.71 Score on a scale Standard Error 1.19

SECONDARY outcome

Timeframe: 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.

Population: All participants with at least one on-treatment ISLT immediate recall evaluation available. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=20 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=20 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=41 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
International Shopping List Test (ISLT) - Immediate Recall Change from baseline to week 8	2.11 Scores on a scale Standard Error 1.66	-0.75 Scores on a scale Standard Error 1.37	0.41 Scores on a scale Standard Error 0.65
International Shopping List Test (ISLT) - Immediate Recall Change from baseline to week 4	0.29 Scores on a scale Standard Error 1.08	-1.24 Scores on a scale Standard Error 0.61	0.11 Scores on a scale Standard Error 0.54
International Shopping List Test (ISLT) - Immediate Recall Change from baseline to week 16	0.30 Scores on a scale Standard Error 1.04	0.11 Scores on a scale Standard Error .99	-0.15 Scores on a scale Standard Error .46

SECONDARY outcome

Timeframe: 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.

Population: All subjects with a baseline and at least one on-treatment TUG evaluation. As placebo given twice or three times a day would not be expected to differences in outcome, per the protocol and statistical analysis plan (SAP) the placebo group was considered as one group, regardless of whether they received placebo BID or TID.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=20 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=20 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=37 Participants 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Timed Up and Go Test (TUG) Week 8	-0.2 Seconds Standard Error 0.5	1.0 Seconds Standard Error 0.9	0.4 Seconds Standard Error 0.4
Timed Up and Go Test (TUG) Week 16	-1.4 Seconds Standard Error 1.0	1.3 Seconds Standard Error 0.7	1.5 Seconds Standard Error 0.9

SECONDARY outcome

Timeframe: 16 weeks

Population: All subjects with a baseline and week 16 EEG recording.

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.

Outcome measures

Outcome measures
Measure	Neflamapimod TID n=6 Participants 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=12 Participants 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe	0.24 Hz Standard Deviation 1.06	0.36 Hz Standard Deviation 0.95	—

Adverse Events

Neflamapimod TID

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Neflamapimod BID

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 17 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Neflamapimod TID n=20 participants at risk 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=26 participants at risk 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=45 participants at risk 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Nervous system disorders New brain lesions of unclear etiology	0.00% 0/20 • 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.	3.8% 1/26 • Number of events 1 • 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.	0.00% 0/45 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diagnosis of brain tumor	0.00% 0/20 • 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.	3.8% 1/26 • Number of events 1 • 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.	0.00% 0/45 • 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.
Injury, poisoning and procedural complications Head injury	0.00% 0/20 • 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.	3.8% 1/26 • Number of events 1 • 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.	0.00% 0/45 • 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.
Gastrointestinal disorders Hematochezia	0.00% 0/20 • 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.	0.00% 0/26 • 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.	2.2% 1/45 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Asthma exacerbation	0.00% 0/20 • 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.	0.00% 0/26 • 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.	2.2% 1/45 • Number of events 1 • 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.
Nervous system disorders Intraparenchymal hemorrhage	0.00% 0/20 • 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.	0.00% 0/26 • 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.	2.2% 1/45 • Number of events 1 • 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.
Blood and lymphatic system disorders Internal bleeding	0.00% 0/20 • 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.	0.00% 0/26 • 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.	2.2% 1/45 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Neflamapimod TID n=20 participants at risk 40 mg capsules administered orally TID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg	Neflamapimod BID n=26 participants at risk 40 mg capsules administered orally BID with food for 16 weeks; subjects followed the BID regimen if Screening weight was \<80 kg	Placebo n=45 participants at risk 40 mg matching placebo capsules administered orally TID or BID with food for 16 weeks; subjects followed the TID regimen if Screening weight was ≥80 kg and the BID regimen if Screening weight was \<80 kg
Gastrointestinal disorders Diarrhea	15.0% 3/20 • Number of events 3 • 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.	0.00% 0/26 • 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.	11.1% 5/45 • Number of events 5 • 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.
Gastrointestinal disorders Nausea	5.0% 1/20 • Number of events 1 • 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.	7.7% 2/26 • Number of events 2 • 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.	6.7% 3/45 • Number of events 3 • 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.
Injury, poisoning and procedural complications Fall	5.0% 1/20 • Number of events 1 • 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.	19.2% 5/26 • Number of events 5 • 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.	8.9% 4/45 • Number of events 5 • 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.
Nervous system disorders Headache	15.0% 3/20 • Number of events 3 • 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.	3.8% 1/26 • Number of events 1 • 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.	4.4% 2/45 • Number of events 3 • 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.
Nervous system disorders Tremor	0.00% 0/20 • 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.	0.00% 0/26 • 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.	6.7% 3/45 • Number of events 3 • 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.

Additional Information

Dr. John Alam

EIP Pharma

Phone: 6176698426

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place