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CompletedNCT03402659REVERSE-SDUpdated Oct 27, 2021Results posted

Proof-of-Concept Study of a Selective p38 MAPK Alpha Inhibitor, Neflamapimod, in Subjects With Mild Alzheimer's Disease

A Phase 2 interventional study of neflamapimod and placebo in Alzheimer Disease, sponsored by EIP Pharma Inc. Completed at 38 sites in 5 countries. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-10-27.

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

Phase
Phase 2
Study type
Interventional
Enrollment
161
Allocation
Randomized
Ages
55 Years to 85 Years
Sex
All
01

Study 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.

Read the detailed description

Details provided elsewhere.

02

Conditions studied

  • Alzheimer Disease

Browse trials for

03

Who can participate

Ages eligible
55 Years to 85 Years
Sexes eligible
All
Accepts 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

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.
04

Study design

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

Study arms

  • Experimental
    neflamapimod

    40 mg hard gelatin capsules, taken twice daily with food.

    Drug: neflamapimod

  • Placebo comparator
    placebo

    hard gelatin capsules containing excipients only, weight- and size-matched; taken twice daily with food.

    Other: placebo

Interventions

  • Drugneflamapimod

    40 mg neflamapimod capsule

    Also known as: VX-745

  • Otherplacebo

    matching placebo capsule

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

06

Results

Posted Oct 27, 2021

Participant flow

Participant flow — Overall Study
MilestonePlacebo ArmNeflamapimod Arm
Started8378
Completed7873
Not completed55

Outcome measures

PrimaryTotal 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
Reported as:
Mean · Z-score
Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R)
Z-scorePlacebo ArmNeflamapimod Arm
Total and Delayed Recall on the Hopkins Verbal Learning Test - Revised (HVLT-R)-0.09679 ± 0.074840-0.15776 ± 0.085805
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · Mixed Models Analysis · p = 0.564 · Mean difference (final values): -0.06098 · 95% CI -0.26973 to 0.14777
SecondaryWechsler 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
Reported as:
Mean · Scores on a scale
Wechsler Memory Scale (WMS) Immediate and Delayed Recall
Scores on a scalePlacebo ArmNeflamapimod Arm
Wechsler Memory Scale (WMS) Immediate and Delayed Recall16.6 ± 2.0916.0 ± 2.07
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · Mixed Models Analysis · p = 0.823 · Mean difference (final values): -0.6 · 95% CI -6.0 to 4.8
SecondaryClinical 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
Reported as:
Mean · Scores on a scale
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
Scores on a scalePlacebo ArmNeflamapimod Arm
Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)1.0 ± 0.201.1 ± 0.21
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · Mixed Models Analysis · p = 0.806 · Mean difference (final values): 0.1 · 95% CI -0.4 to 0.6
SecondaryMini-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)
Reported as:
Mean · Scores on a scale
Mini-Mental State Examination (MMSE)
Scores on a scalePlacebo ArmNeflamapimod Arm
Mini-Mental State Examination (MMSE)-0.5 ± 0.31-0.8 ± 0.33
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.489 · Mean difference (final values): -0.3 · 95% CI -1.0 to 0.5
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Total Tau
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Total Tau10.0 ± 6.83-8.6 ± 7.36
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.031 · Mean difference (final values): -18.8 · 95% CI -35.8 to -1.8
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Phospho-tau
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Phospho-tau0.9 ± 0.63-1.1 ± 0.68
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.012 · Mean difference (final values): -2.0 · 95% CI -3.6 to -0.5
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Amyloid Beta 1-40
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Amyloid Beta 1-40399.7 ± 249.18282.3 ± 268.58
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.709 · Mean difference (final values): -117.4 · 95% CI -738.9 to 504.2
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Amyloid Beta 1-42
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Amyloid Beta 1-4231.1 ± 12.7010.0 ± 13.75
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.192 · Mean difference (final values): -21.0 · 95% CI -52.7 to 10.7
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Neurogranin
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Neurogranin11.1 ± 9.16-9.9 ± 9.82
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.068 · Mean difference (final values): -21.0 · 95% CI -43.6 to 1.6
SecondaryCerebrospinal 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
Reported as:
Mean · pg/mL
Cerebrospinal Fluid Neurofilament Light Chain
pg/mLPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid Neurofilament Light Chain231.9 ± 61.31121.7 ± 66.92
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.156 · Mean difference (final values): -110.1 · 95% CI -262.7 to 42.4
SecondaryCerebrospinal 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
Reported as:
Mean · ratio
Cerebrospinal Fluid P-tau/AB1-42 Ratio
ratioPlacebo ArmNeflamapimod Arm
Cerebrospinal Fluid P-tau/AB1-42 Ratio-0.0 ± 0-0.0 ± 0
Statistical analysis
  • Placebo Arm vs Neflamapimod Arm · ANCOVA · p = 0.590 · Mean difference (final values): -0.0 · 95% CI -0.0 to 0.0

Adverse events

Collected over Up to 29 weeks. AEs occurring from when the subject signed the ICF until up to 30 days after the last dose were collected. 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
Placebo Arm0/83 (0%)3/83 (3.6%)16/83 (19.3%)
Neflamapimod Arm0/78 (0%)2/78 (2.6%)18/78 (23.1%)
Most frequent serious events
Most frequent serious events
EventPlacebo ArmNeflamapimod Arm
Multiple MyelomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/831/78
HypokalemiaMetabolism and nutrition disorders0/831/78
Non-Cardiac Chest PainGeneral disorders1/830/78
PneumoniaInfections and infestations1/830/78
FallInjury, poisoning and procedural complications1/830/78
Most frequent other events
Most frequent other events
EventPlacebo ArmNeflamapimod Arm
Upper Respiratory Tract InfectionInfections and infestations7/834/78
FallInjury, poisoning and procedural complications3/835/78
HeadacheNervous system disorders4/835/78
DiarrheaGastrointestinal disorders2/834/78

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Placebo ArmNeflamapimod ArmTotal
<=18 years000
Between 18 and 65 years141630
>=65 years6962131
Age, Continuous
Age, Continuous(years)Placebo ArmNeflamapimod ArmTotal
Mean72.6 (56 to 85)70.8 (56 to 84)71.8 (56 to 85)
Sex: Female, Male
Sex: Female, Male(Participants)Placebo ArmNeflamapimod ArmTotal
Female433780
Male404181
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo ArmNeflamapimod ArmTotal
American Indian or Alaska Native000
Asian112
Native Hawaiian or Other Pacific Islander000
Black or African American303
White7977156
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Placebo ArmNeflamapimod ArmTotal
Netherlands101020
United States383573
Czechia369
Denmark347
United Kingdom292352
Weight
Weight(Kg)Placebo ArmNeflamapimod ArmTotal
Mean74.4 (45 to 111)75.6 (48.9 to 161)75 (45 to 161)
07

Study locations

38 sites
  • Alliance for Research
    Long Beach, California 90807, United States
  • Pacific Research Network
    San Diego, California 92103, United States
  • CITrials
    Santa Ana, California 92705, United States
  • Southern California Research, LLC
    Simi Valley, California 93065, United States
  • Viking Clinical Research
    Temecula, California 92591, United States
  • Miami Dade Medical Research Institute
    Miami, Florida 33176, United States
  • Sensible Healthcare, LLC
    Ocoee, Florida 34761, United States
  • Anchor Neuroscience
    Pensacola, Florida 32502, United States
  • Progressive Medical Research
    Port Orange, Florida 32127, United States
  • Suncoast Neuroscience Associates, Inc.
    Saint Petersburg, Florida 33713, United States
  • Florida Premier Research Institute
    Winter Park, Florida 32789, United States
  • Northwest Clinical Trials
    Boise, Idaho 83704, United States
  • MassGeneral Institute for Neurodegenerative Disease
    Charlestown, Massachusetts 02129, United States
  • Manhattan Behavioral Medicine
    New York, New York 10036, United States
  • Alzheimer's Memory Center and Research Institute
    Charlotte, North Carolina 28270, United States
  • Northwest Clinical Research Center
    Seattle, Washington 98007, United States
  • Neuro HK, s.r.o. POLIKLINIKA CHOCEŇ, a.s.
    Choceň, 565 01, Czechia
  • Cerebrovaskulární poradna s.r.o.
    Moravská Ostrava, 702 00, Czechia
  • Clintrial S.R.O
    Prague, 100 00, Czechia
  • Private Psychiatric Centre
    Prague, 109 00, Czechia
  • Vestra Clinics S.R.O
    Rychnov Nad Kněžnou, 516 01, Czechia
  • CCBR Clinical Research, Aalborg
    Aalborg, DK-9000, Denmark
  • CCBR Clinical Research, Ballerup
    Ballerup, DK-2750, Denmark
  • CCBR Clinical Research, Vejle
    Vejle, DK-7100, Denmark
  • Jeroen Bosch Ziekenhuis
    's-Hertogenbosch, 5223 GZ, Netherlands
  • Alzheimer Research Center
    Amsterdam, 1081 GM, Netherlands
  • Amphia Ziekhuis
    Breda, 4817 CK, Netherlands
  • MAC Clinical Research Tankersley
    Barnsley, S75 3DL, United Kingdom
  • Re:Cognition Health Birmingham
    Birmingham, B16 8LT, United Kingdom
  • MAC Clinical Research Blackpool
    Blackpool, FY2 0JH, United Kingdom
  • Fulbourn Hospital
    Cambridge, CB21 5EF, United Kingdom
  • MAC Clinical Research Leeds
    Leeds, LS10 1DU, United Kingdom
  • MAC Clinical Research Liverpool
    Liverpool, L34 1BH, United Kingdom
  • Re:Cognition Health London
    London, W1G 9JF, United Kingdom
  • St. Pancras Clinical Research
    London, WC1X 8QD, United Kingdom
  • MAC Clinical Research Manchester
    Manchester, M13 9NQ, United Kingdom
  • Re:Cognition Health Plymouth
    Plymouth, PL5 8BT, United Kingdom
  • 5 Boroughs/North West Boroughs Healthcare NHS Foundation Trust
    Warrington, WA22 8WA, United Kingdom
08

References and documents

Publications

  • Prins ND, Harrison JE, Chu HM, Blackburn K, Alam JJ, Scheltens P; REVERSE-SD Study Investigators. A phase 2 double-blind placebo-controlled 24-week treatment clinical study of the p38 alpha kinase inhibitor neflamapimod in mild Alzheimer's disease. Alzheimers Res Ther. 2021 May 27;13(1):106. doi: 10.1186/s13195-021-00843-2. PubMed 34044875 ↗
  • Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11. PubMed 33974419 ↗

Study documents

  • Study protocol · Aug 27, 2018
  • Statistical analysis plan · Jul 30, 2019

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
NCT03402659
Lead sponsor
EIP Pharma Inc
Collaborators
Worldwide Clinical Trials, Amsterdam UMC, location VUmc
Responsible party
Sponsor
First posted
Jan 18, 2018
Start date
Dec 29, 2017
Primary completion
Jun 30, 2019
Completion
Jul 31, 2019
Results posted
Oct 27, 2021
Last update
Oct 27, 2021

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 ↗

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This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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