Clinical Study of Neflamapimod in Patients With Primary Progressive Aphasia

NCT07033481 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CRVO24-NFD-701
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

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

Outcome Measures

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.

  Baseline to Week 36

Other Outcomes (8)

• Change from Baseline to Week 36 in Digitized Speech Metrics

  Baseline to Week 36

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

  Baseline to Week 36

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

  Baseline to Week 36

Study Arms (2)

Neflamapimod

EXPERIMENTAL

Drug: Neflamapimod

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Neflamapimod DRUG

Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40 mg capsules

Neflamapimod

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EIP Pharma Inc: lead
• CervoMed, Inc: collaborator

Study Sites (7)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

ACTIVE NOT RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Columbia University

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

The Ohio State University

Columbus, Ohio, 43221, United States

ACTIVE NOT RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

ACTIVE NOT RECRUITING

Windsor Research Unit, Fulbourn Hospital

Cambridge, CB21 5EF, United Kingdom

RECRUITING

Clinical Ageing Research Unit, Campus for Ageing and Vitality, Biomedical Research Building

Newcastle upon Tyne, NE4 5PL, United Kingdom

RECRUITING

MeSH Terms

Conditions

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Neurodegenerative Diseases; Aphasia; Language Disorders; Frontotemporal Dementia; Speech; Aphasia, Primary Progressive

Condition Hierarchy (Ancestors)

Speech Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Frontotemporal Lobar Degeneration; Dementia; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Verbal Behavior; Communication; Behavior

Central Study Contacts

Amanda Gardner

CONTACT

973-452-1121; am.gardner@cervomed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants will be assigned 40 milligram (mg) neflamapimod three times per day (TID) 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.

Study Record Dates

• First Submitted: June 13, 2025
• First Posted: June 24, 2025
• Study Start: October 2, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); GB (2)