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Active, not recruitingNCT07033481Updated Jul 6, 2026

Clinical Study of Neflamapimod in Patients With Primary Progressive Aphasia

A Phase 2 interventional study of Neflamapimod and Placebo in Nonfluent Variant Primary Progressive Aphasia (nfvPPA), sponsored by EIP Pharma Inc. Active, not recruiting at 7 sites in 2 countries. Open to participants aged 40 Years to 85 Years. Per ClinicalTrials.gov, last updated 2026-07-06.

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

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
40 Years to 85 Years
Sex
All
01

Study summary

The goal of this exploratory study is to evaluate the effect of neflamapimod in participants with nonfluent variant primary progressive aphasia (nfvPPA). We aim to evaluate the safety, pharmacokinetics and clinical effects of neflamapimod of participants with nfvPPA.

02

Conditions studied

  • Nonfluent Variant Primary Progressive Aphasia (nfvPPA)

Keywords

  • Brain Diseases
  • Central Nervous System Diseases
  • Nervous System Diseases
  • Neurocognitive Disorders
  • Mental Disorders
  • Neurodegenerative Diseases
  • Aphasia
  • Language Disorder
  • Frontotemporal Dementia
  • Speech and Language Disorder
  • Primary Progressive Aphasia
03

Who can participate

Ages eligible
40 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Men and women aged 40-85 years at Screening.
  • Participant or participant's legally authorized representative (where applicable) is willing and able to provide written informed consent.
  • Clinical diagnosis of nfvPPA by consensus criteria [Gorno-Tempini et al, 2011].

    • At least one of the following core features must be present:

      1. Agrammatism in language production
      2. Effortful, halting speech with inconsistent speech sound errors and distortions (apraxia of speech)
    • At least 2 of 3 of the following other features must be present:

      1. Impaired comprehension of syntactically complex sentences
      2. Spared single-word comprehension
      3. Spared object knowledge
  • Global CDR® plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration (NACC FTLD) score of 0.5 or 1 during Screening.
  • CDR® plus NACC FTLD language domain score of 0.5, 1 or 2 during Screening.
  • Normal or corrected eyesight and auditory abilities, sufficient to perform all aspects of the study scales and assessments.
  • Fluent in English, per Investigator judgement.
  • Must have reliable study partner that is able to attend all study visits with participant. Study partner must be able to read, write, and understand the English language.

Exclusion criteria

Exclusion Criteria:

  • Brain Magnetic Resonance Image (MRI) incompatible with a diagnosis of nfvPPA.
  • History or evidence of a central nervous system (CNS) condition other than nfvPPA which may cause symptoms of aphasia or dementia, including but not limited to Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), inflammatory/demyelinating CNS conditions, Creutzfeldt Jakob disease, vascular dementia, post-stroke dementia, etc.
  • Features or Parkinsonism, corticobasal syndrome or progressive supranuclear palsy that are as or more prominent than the language features of nfvPPA, and/or motor features which are sufficiently severe that they could significantly impact performance on any of the clinical or neuropsychological measures.
  • Plasma pTau217 result with a high likelihood of the presence of amyloid pathology at Screening or documented evidence of positive biomarkers associated with Alzheimer's disease pathology (e.g., abnormal plasma Aβ42/40 ratio, abnormal CSF phospo-tau/amyloid ratio, or presence of amyloid tracer update on brain amyloid positron emission tomography [PET] imaging).
  • Known progranulin (GRN) mutations.
  • Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
  • Metabolic or toxic encephalopathy or dementia due to a general medical condition.
  • History of previous neurosurgery to the brain within the past five years.
  • 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.
  • Clinically relevant intellectual impairment that may interfere with the ability to complete the study scales and assessments, at the discretion of the Investigator.
  • Diagnosis of alcohol or drug abuse within the previous 2 years.
  • Poorly controlled clinically significant medical illness, such as hypertension; myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would interfere with assessment of drug safety.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5.

    • If participant has a documented history of Gilbert's syndrome, criterion of total bilirubin >1.5 x ULN is not applicable.
    • If participant is taking anticoagulants (e.g., warfarin), and has no known liver issues, INR >3.
  • Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
  • Participated in a study of an investigational drug or transcranial direct current stimulation less than 6 weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
  • Male with female partner(s) of childbearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
  • Female of childbearing potential (see Section 5.10), with a positive pregnancy test result during Screening and are unwilling or unable to adhere to contraception requirements specified in the protocol.
  • Weight less than 50 kg at Screening.

The following additional exclusion criteria applies for participants undergoing (18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography) 18F-FDG PET-CT (18F-FDG PET-CT scans are optional):

  • Blood glucose levels >200 mg/dL.
  • Contraindications to having a PET scan.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
20 participants (estimated)

Study arms

  • Experimental
    Neflamapimod

    Drug: Neflamapimod

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

  • DrugNeflamapimod

    Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α)

  • DrugPlacebo

    Placebo is a capsule that looks just like neflamapimod but without the active ingredients

05

What researchers measure

Primary outcomes

  1. Incidence of Adverse Events and Serious Adverse Events.

    The number and proportion of participants experiencing adverse events (AEs) and serious adverse events (SAEs) during the study period, categorized by severity and relationship to the study intervention.

    Time frame: Baseline to Week 36

Other outcomes

  1. Change from Baseline to Week 36 in Digitized Speech Metrics

    Participant will complete a series of tasks in which voice recordings will be captures. The voice recording will be analyzed for linguistic and acoustic metrics.

    Time frame: Baseline to Week 36

  2. Change from Baseline to Week 36 in Letter Fluency Test (LFT)

    The LFT is scored by counting the number of valid words a participant generates within a set time. Scores can range from 0 to 50. Higher scores indicate better verbal fluency and cognitive processing, while lower scores reflect difficulty in language, memory, and executive functioning.

    Time frame: Baseline to Week 36

  3. Change from Baseline to Week 36 in Category Fluency Test (CFT)

    The CFT is scored by counting the number of valid words a participant generates with in a specific category in a set time. Higher scores indicate better semantic memory and executive functioning, while lower scores reflect impairments in cognitive processing or language abilities.

    Time frame: Baseline to Week 36

  4. Change from Baseline to Week 36 in Stroop Color and Word Test (SCWT)

    The SCWT is scored based on the time taken to complete each of the four conditions and are scaled utilizing a norming method based upon participant age. Scaled scores range from 1 to 19. Faster times, and higher scaled scores, indicate stronger executive function.

    Time frame: Baseline to Week 36

  5. Change from Baseline to Week 36 in Progressive Aphasia Severity Scale (PASS)

    The PASS is a tool for rating the presence and severity of symptoms across speech, language and functional communication domains in participants with progressive aphasia. Individual domain scores range from 0 (normal) to 3 (severe impairment). Each individual domain is summed to provide a PASS Sum of Boxes Score. A higher PASS Sum of Boxes Score indicates greater severity of symptoms.

    Time frame: Baseline to Week 36

  6. Change from Baseline to Week 36 in Northwestern Anagram Test (NAT)

    The NAT examines non-verbal production of subject extracted wh-questions (SWh) and object extracted wh-questions (OWh). Scores for the NAT range from 0-10 (5 points each SWh- and OWh-Questions). A higher total score indicates better non-verbal sentence production, while a lower score reflects worse non-verbal sentence production.

    Time frame: Baseline to Week 36

  7. Change from Baseline to Week 36 in Western Aphasia Battery-Revised (WAB-R)

    The WAB-R is a test designed to assess a participant's language impairment. The WAB-R measures both linguistic and non-linguistic skills. The core measure of aphasia is the Aphasia Quotient (AQ) and is derived from the Spontaneous Speech, Auditory Verbal Comprehension, Repetition, Naming and Word Finding section scores. The AQ can range from 0 to 100 with higher scores indicating milder language impairment and the lower scores indicating greater language impairment.

    Time frame: Baseline to Week 36

  8. Change from Baseline to Week 36 in Clinical Dementia Rating Plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Sum of Boxes (CDR® plus NACC FTLD-SB)

    The CDR® plus NACC FTLD is aimed at evaluating those suffering from or at risk for any of the forms of frontotemporal lobar degeneration. The CDR® plus NACC FTLD-SB is scored by summing ratings across 10 domains. Each domain is rated on a scale from 0 (no impairment) to 3 (serve impairment). The total score ranges from 0 to 30, where higher scores indicate greater cognitive and functional impairment.

    Time frame: Baseline to Week 36

06

Study locations

7 sites
  • Northwestern Memorial Hospital
    Chicago, Illinois 60611, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Columbia University
    New York, New York 10032, United States
  • The Ohio State University
    Columbus, Ohio 43221, United States
  • Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Windsor Research Unit, Fulbourn Hospital
    Cambridge, CB21 5EF, United Kingdom
  • Clinical Ageing Research Unit, Campus for Ageing and Vitality, Biomedical Research Building
    Newcastle upon Tyne, NE4 5PL, United Kingdom
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07033481
Lead sponsor
EIP Pharma Inc
Collaborators
CervoMed, Inc.
Responsible party
Sponsor
First posted
Jun 24, 2025
Start date
Oct 2, 2025
Primary completion
Sep 2026 (estimated)
Completion
Oct 2026 (estimated)
Last update
Jul 6, 2026

Oversight

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

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