Alzheimer Disease
Conditions
Brief summary
This is a phase 2b, double-blind, placebo controlled proof-of-concept study of a an oral small molecule selective inhibitor of p38 alpha kinase, neflamapimod, administered for 24 weeks in subjects with mild Alzheimer's disease. The primary objective is to demonstrate significant improvement relative to placebo-treatment in episodic memory function, as assessed by the Hopkins Verbal Learning Test. Secondary endpoints include Clinical Dementia Rating scale (CDR), Wechsler Memory Scale (WMS), Mini-Mental-Status-Examination (MMSE) and Cerebrospinal fluid (CSF) biomarkers of AD disease activity and progression.
Detailed description
Details provided elsewhere.
Interventions
DRUGneflamapimod
40 mg neflamapimod capsule
OTHERplacebo
matching placebo capsule
Sponsors
Worldwide Clinical Trials
Amsterdam UMC, location VUmc
EIP Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women age 55 to 85 years, inclusive. 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
1. Evidence that the primary basis for cognitive impairment is neurodegenerative disease other than AD, including, but not limited to, vascular dementia, dementia with Lewy bodies, and Parkinson's disease. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) | Baseline and 24 weeks | Combined change from baseline in z-scores of total and delayed recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) in neflamapimod-treated subjects compared to placebo. The primary endpoint was analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. For baseline total and delayed recall, a z-score for each subject is defined by z=(x-m)/s where x is the subject's recall at baseline, and m and s are the overall mean and overall standard deviation of recall at baseline across all subjects. A composite baseline z-score for each subject is calculated using equal weighting in the following way: Z=0.5\*z-score for total recall at baseline + 0.5\*z-score for delayed recall at baseline. For HVLT-R, higher score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | Baseline and 24 weeks | Change from baseline in total score of Clinical Dementia Rating Scale - Sum of Boxes (range 0-18) in neflamapimod-treated subjects compared to placebo. CDR-SB scores were analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. CDR-SB score is calculated by adding the individual scores from 6 domains, Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. CDR-SB scores range from 0-18, where a lower score indicates improvement. The scale is administered in a semi-structured interview format with both the patient and the caregiver/informant. |
| Mini-Mental State Examination (MMSE) | Baseline and 26 Weeks (Follow-up visit, 2 weeks from end of dosing) | Changes from baseline in Mini-Mental State Examination (MMSE) scores were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. The MMSE is scored from 0-30 with a higher score indicating improvement. The MMSE includes questions that test orientation, attention, memory, language and visual-spatial skills. |
| Cerebrospinal Fluid Total Tau | Baseline and 24 weeks | Change from, baseline in Total Tau (t-tau) were compared using an ANCOVA with treatment group, background ADspecific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Cerebrospinal Fluid Phospho-tau | Baseline and 24 weeks | Change from baseline in Phospho-Tau (p-tau181) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Wechsler Memory Scale (WMS) Immediate and Delayed Recall | Baseline and 24 weeks | Change from baseline in Wechsler Memory Scale(WMS) immediate and delayed recall composites in neflamapimod-treated subjects compared to placebo. WMS scores were analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. Composite scores for immediate and delayed recall are the combination of all immediate and delayed recall task raw scores and ranges from 0-228. A higher score indicates improvement. The following tests in WMS are done both for immediate and delayed recall: Logical Memory test, in which subject is read a story; Verbal-Paired Associates, in which subject is given pairs of words and asked remember which words go together; and Visual Reproduction, in which subject is given drawings of specific shapes |
| Cerebrospinal Fluid Amyloid Beta 1-42 | Baseline and 24 weeks | Change from baseline in Amyloid beta (AB1-42) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Cerebrospinal Fluid Neurogranin | Baseline and 24 weeks | Change from baseline in Neurogranin were compared using an ANCOVA with treatment group, background ADspecific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Cerebrospinal Fluid Neurofilament Light Chain | Baseline and 24 weeks | Change from baseline in Neurofilament Light Chain (NFL) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Cerebrospinal Fluid P-tau/AB1-42 Ratio | Baseline and 24 weeks | Changes in the ratio of Phospho-Tau/Amyloid Beta (p-tau181/AB1-42) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
| Cerebrospinal Fluid Amyloid Beta 1-40 | Baseline and 24 weeks | Change from baseline in Amyloid beta (AB1-40) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. |
Countries
Czechia, Denmark, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Arm Arm of trial including the 83 subjects that were randomly assigned (1:1) to take placebo | 83 |
| Neflamapimod Arm Arm of trial including the 78 subjects that were randomly assigned (1:1) to take neflamapimod (active study drug). | 78 |
| Total | 161 |
Baseline characteristics
| Characteristic | Placebo Arm | Neflamapimod Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 69 Participants | 62 Participants | 131 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 16 Participants | 30 Participants |
| Age, Continuous | 72.6 years | 70.8 years | 71.8 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 79 Participants | 77 Participants | 156 Participants |
| Region of Enrollment Czechia | 3 participants | 6 participants | 9 participants |
| Region of Enrollment Denmark | 3 participants | 4 participants | 7 participants |
| Region of Enrollment Netherlands | 10 participants | 10 participants | 20 participants |
| Region of Enrollment United Kingdom | 29 participants | 23 participants | 52 participants |
| Region of Enrollment United States | 38 participants | 35 participants | 73 participants |
| Sex: Female, Male Female | 43 Participants | 37 Participants | 80 Participants |
| Sex: Female, Male Male | 40 Participants | 41 Participants | 81 Participants |
| Weight | 74.4 Kg | 75.6 Kg | 75 Kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 78 |
| other Total, other adverse events | 16 / 83 | 18 / 78 |
| serious Total, serious adverse events | 3 / 83 | 2 / 78 |
Outcome results
Primary
Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R)
Combined change from baseline in z-scores of total and delayed recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) in neflamapimod-treated subjects compared to placebo. The primary endpoint was analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. For baseline total and delayed recall, a z-score for each subject is defined by z=(x-m)/s where x is the subject's recall at baseline, and m and s are the overall mean and overall standard deviation of recall at baseline across all subjects. A composite baseline z-score for each subject is calculated using equal weighting in the following way: Z=0.5\*z-score for total recall at baseline + 0.5\*z-score for delayed recall at baseline. For HVLT-R, higher score indicates improvement.
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) | -0.09679 Z-score | Standard Error 0.07484 |
| Neflamapimod Arm | Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) | -0.15776 Z-score | Standard Error 0.085805 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.56495% CI: [-0.26973, 0.14777]Mixed Models Analysis
Secondary
Cerebrospinal Fluid Amyloid Beta 1-40
Change from baseline in Amyloid beta (AB1-40) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Amyloid Beta 1-40 | 399.7 pg/mL | Standard Error 249.18 |
| Neflamapimod Arm | Cerebrospinal Fluid Amyloid Beta 1-40 | 282.3 pg/mL | Standard Error 268.58 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.70995% CI: [-738.9, 504.2]ANCOVA
Secondary
Cerebrospinal Fluid Amyloid Beta 1-42
Change from baseline in Amyloid beta (AB1-42) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Amyloid Beta 1-42 | 31.1 pg/mL | Standard Error 12.7 |
| Neflamapimod Arm | Cerebrospinal Fluid Amyloid Beta 1-42 | 10.0 pg/mL | Standard Error 13.75 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.19295% CI: [-52.7, 10.7]ANCOVA
Secondary
Cerebrospinal Fluid Neurofilament Light Chain
Change from baseline in Neurofilament Light Chain (NFL) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants with analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Neurofilament Light Chain | 231.9 pg/mL | Standard Error 61.31 |
| Neflamapimod Arm | Cerebrospinal Fluid Neurofilament Light Chain | 121.7 pg/mL | Standard Error 66.92 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.15695% CI: [-262.7, 42.4]ANCOVA
Secondary
Cerebrospinal Fluid Neurogranin
Change from baseline in Neurogranin were compared using an ANCOVA with treatment group, background ADspecific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants with analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Neurogranin | 11.1 pg/mL | Standard Error 9.16 |
| Neflamapimod Arm | Cerebrospinal Fluid Neurogranin | -9.9 pg/mL | Standard Error 9.82 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.06895% CI: [-43.6, 1.6]ANCOVA
Secondary
Cerebrospinal Fluid Phospho-tau
Change from baseline in Phospho-Tau (p-tau181) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Phospho-tau | 0.9 pg/mL | Standard Error 0.63 |
| Neflamapimod Arm | Cerebrospinal Fluid Phospho-tau | -1.1 pg/mL | Standard Error 0.68 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.01295% CI: [-3.6, -0.5]ANCOVA
Secondary
Cerebrospinal Fluid P-tau/AB1-42 Ratio
Changes in the ratio of Phospho-Tau/Amyloid Beta (p-tau181/AB1-42) were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants with analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid P-tau/AB1-42 Ratio | -0.0 ratio | Standard Error 0 |
| Neflamapimod Arm | Cerebrospinal Fluid P-tau/AB1-42 Ratio | -0.0 ratio | Standard Error 0 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.5995% CI: [0, 0]ANCOVA
Secondary
Cerebrospinal Fluid Total Tau
Change from, baseline in Total Tau (t-tau) were compared using an ANCOVA with treatment group, background ADspecific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value.
Time frame: Baseline and 24 weeks
Population: All participants with analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Cerebrospinal Fluid Total Tau | 10.0 pg/mL | Standard Error 6.83 |
| Neflamapimod Arm | Cerebrospinal Fluid Total Tau | -8.6 pg/mL | Standard Error 7.36 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.03195% CI: [-35.8, -1.8]ANCOVA
Secondary
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
Change from baseline in total score of Clinical Dementia Rating Scale - Sum of Boxes (range 0-18) in neflamapimod-treated subjects compared to placebo. CDR-SB scores were analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. CDR-SB score is calculated by adding the individual scores from 6 domains, Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. CDR-SB scores range from 0-18, where a lower score indicates improvement. The scale is administered in a semi-structured interview format with both the patient and the caregiver/informant.
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 1.0 Scores on a scale | Standard Error 0.2 |
| Neflamapimod Arm | Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) | 1.1 Scores on a scale | Standard Error 0.21 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.80695% CI: [-0.4, 0.6]Mixed Models Analysis
Secondary
Mini-Mental State Examination (MMSE)
Changes from baseline in Mini-Mental State Examination (MMSE) scores were compared using an ANCOVA with treatment group, background AD-specific therapy, CDR-Global Score as main effects and the baseline assessment as the covariate. The results of the ANCOVA are summarized using the treatment groups' least square means, the difference between the treatment groups' least square means, the 95% confidence interval for the treatment group difference and the p-value. The MMSE is scored from 0-30 with a higher score indicating improvement. The MMSE includes questions that test orientation, attention, memory, language and visual-spatial skills.
Time frame: Baseline and 26 Weeks (Follow-up visit, 2 weeks from end of dosing)
Population: All participants who had analyzable results at Baseline and Follow-up Visit (2 weeks post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Mini-Mental State Examination (MMSE) | -0.5 Scores on a scale | Standard Error 0.31 |
| Neflamapimod Arm | Mini-Mental State Examination (MMSE) | -0.8 Scores on a scale | Standard Error 0.33 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.48995% CI: [-1, 0.5]ANCOVA
Secondary
Wechsler Memory Scale (WMS) Immediate and Delayed Recall
Change from baseline in Wechsler Memory Scale(WMS) immediate and delayed recall composites in neflamapimod-treated subjects compared to placebo. WMS scores were analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. Composite scores for immediate and delayed recall are the combination of all immediate and delayed recall task raw scores and ranges from 0-228. A higher score indicates improvement. The following tests in WMS are done both for immediate and delayed recall: Logical Memory test, in which subject is read a story; Verbal-Paired Associates, in which subject is given pairs of words and asked remember which words go together; and Visual Reproduction, in which subject is given drawings of specific shapes
Time frame: Baseline and 24 weeks
Population: All participants who had analyzable results at Baseline and Week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Arm | Wechsler Memory Scale (WMS) Immediate and Delayed Recall | 16.6 Scores on a scale | Standard Error 2.09 |
| Neflamapimod Arm | Wechsler Memory Scale (WMS) Immediate and Delayed Recall | 16.0 Scores on a scale | Standard Error 2.07 |
Comparison: Mean change from baseline neflamapimod vs placebop-value: 0.82395% CI: [-6, 4.8]Mixed Models Analysis