Nonfluent Variant Primary Progressive Aphasia (nfvPPA)Phase 2NCT07033481
Clinical Study of Neflamapimod in Patients With Primary Progressive Aphasia
A Phase 2 study testing Neflamapimod in people with Nonfluent Variant Primary Progressive Aphasia (nfvPPA), run by EIP Pharma Inc at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
- What is being tested?
- Neflamapimod
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 2 Oct 2025to Oct 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Agrammatism in language production
- Effortful, halting speech with inconsistent speech sound errors and distortions (apraxia of speech)
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- At least 2 of 3 of the following other features must be present:
- Impaired comprehension of syntactically complex sentences
- Spared single-word comprehension
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Northwestern Memorial Hospital
Chicago, Illinois, 60611
The Ohio State University
Columbus, Ohio, 43221
Columbia University
New York, New York, 10032
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
United Kingdom2 sites
Windsor Research Unit, Fulbourn Hospital
Cambridge, CB21 5EF
Clinical Ageing Research Unit, Campus for Ageing and Vitality, Biomedical Research Building
Newcastle upon Tyne, NE4 5PL
About this study
Official title: A Phase 2a Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Primary Progressive Aphasia (PPA)
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.
- Being tested
- Neflamapimod, Placebo
- 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
- Medical subject headings
- Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurocognitive Disorders, Mental Disorders, Neurodegenerative Diseases, Aphasia, Language Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeflamapimodDrug
Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α)
PlaceboDrug
Placebo is a capsule that looks just like neflamapimod but without the active ingredients
| Study group | Role | What they receive |
|---|---|---|
| Neflamapimod | Experimental | Not described Receives: Drug: Neflamapimod |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2025
- Study start2 Oct 2025
- Primary completionSep 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonfluent Variant Primary Progressive Aphasia (nfvPPA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- All participants will be assigned neflamapimod for 24 weeks. Following completion of the 24-week open-label treatment period, participants will continue to a randomized, double-blinded withdrawal period and be randomly assigned on a 1:1 basis to neflamapimod or placebo for 12 weeks.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- EIP Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CervoMed, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07033481
- Sponsor's protocol ID
- CRVO24-NFD-701
- Status last verified
- Jul 2026
- First submitted
- 13 Jun 2025
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No