Clinical trial NCT05869669: RewinD-LB - Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies
Official title: A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Dementia With Lewy Bodies
Keywords: DLB
Lead sponsor: EIP Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
name: Worldwide Clinical Trials
name: CervoMed, Inc
First posted: 2023-05-22
Enrollment: 159
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 2b (hypothesis-testing), multi-center, randomized, double-blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether neflamapimod can improve learning skills, problem solving skills, and memory loss in people diagnosed with DLB. More specifically, improvement in verbal learning, memory, and attention, as well as cognitive and functional performance will be measured.


Eligibility criteria: Inclusion Criteria:

1. Men and women aged ≥55 years.
2. Subject or subject's legally authorized representative is willing and able to provide written informed consent.
3. 3. Probable DLB by consensus criteria (McKeith et al, 2017), including a positive DaTscan™. Specifically, the subject must have the presence of dementia in association with:

   * At least two (2) core clinical features (fluctuating cognition, visual hallucinations, REM sleep disorder, and/or parkinsonism); or
   * One (1) core clinical feature plus an abnormal DaTscan™. Historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), FDG-PET imaging, or MIBG myocardial scintigraphy can take the place of an abnormal DaTscan™ in a patient with only one core clinical feature.
4. CDR Global Score 0.5 (very mild dementia) or 1.0 (mild dementia) during Screening
5. Background dementia therapy:

   * Not currently receiving cholinesterase inhibitor therapy. If the patient received such therapy previously, that therapy must have been discontinued at least 3 months prior to randomization.
   * Receiving cholinesterase inhibitor therapy alone. If the patient is currently receiving cholinesterase inhibitor therapy, the patient must have received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
   * Memantine therapy is allowed, if it had been started at least 3 months prior to randomization and the patient is also receiving cholinesterase inhibitor therapy. If the patient has never been on cholinesterase inhibitor therapy (naïve), then memantine monotherapy is allowed.
6. Normal or corrected eyesight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
7. No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
8. Received vaccination for SARS-CoV-19 unless medical contraindications prevent being vaccinated, or has a history of natural infection.
9. Must have reliable informant or caregiver.

Exclusion Criteria:

1. Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB, including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's disease (AD), or Parkinson's disease (PD).
2. Plasma ptau181 result above the threshold that indicates evidence of pathology associated with Alzheimer's disease at Screening.
3. 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 C-SSRS, or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
4. 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.
5. Diagnosis of alcohol or drug abuse within the previous 2 years.
6. Poorly controlled clinically significant medical illness, such as hypertension (blood pressure \>180 mmHg systolic or 100 mmHg diastolic); 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.
7. 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 patient is taking blood thinners (e.g., warfarin), and has no known liver issues, INR \>3.
8. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
9. Participated in a study of an investigational drug less than six weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
10. History of previous neurosurgery to the brain within the past five years.
11. If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
12. If female who has not has not reached menopause \>1 year previously or has not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.
13. Weight less than 50kg.

All participants who complete the initial 16-week period of the study will be able to continue in the study and receive neflamapimod for an additional 32 weeks (8 months) regardless of whether they received neflamapimod of placebo during the the first 16 weeks.

Primary outcomes:
measure: Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.
timeFrame: 16 weeks
Secondary outcomes:
measure: Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients.
timeFrame: 16 weeks
measure: Change in the composite score of the Neuropsychological Test Battery (NTB), including tests of attention, executive function, and visual learning in neflamapimod-treated subjects compared to placebo recipients.
timeFrame: 16 weeks
measure: Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients.
timeFrame: 16 weeks
Other outcomes:
measure: Exploratory outcome - Dementia Cognitive Fluctuations Scale (DCFS)
timeFrame: 16 weeks
measure: Exploratory outcome - 12-item Neuropsychiatric Inventory (NPI-12)
timeFrame: 16 weeks
measure: Exploratory outcome - Movement Disorder Society - Unified Parkinson's Disease Rating Scale - Part III (MSD-UPDRS3) motor examination (Part III)
timeFrame: 16 weeks
measure: Exploratory outcome - EEG
timeFrame: 16 weeks
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Tucson
country: United States
facility: Banner Alzheimer's Institute - Edson Family Lewy Body Dementia Center
state: Arizona
city: La Jolla
country: United States
facility: UCSD Health Sciences - Movement Disorders Center
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Palo Alto
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: Pasadena
country: United States
facility: SC3 Research Group
state: California
city: Aurora
country: United States
facility: University of Colorado - Dept of Neurology
state: Colorado
city: Washington
country: United States
facility: Georgetown Univ Hospital - Dept of Neurology
state: District of Columbia
city: Lake Worth
country: United States
facility: JEM Research Institute
state: Florida
city: Melbourne
country: United States
facility: ClinCloud
state: Florida
city: Orlando
country: United States
facility: AdventHealth Neuroscience Research
state: Florida
city: Pensacola
country: United States
facility: Panhandle Research and Medical Clinic
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine - Dept of Neurology
state: Maryland
city: Charlestown
country: United States
facility: Mass General Hospital/Harvard Medical School - Dept of Neurology
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Alzheimer's Disease Research Center
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center - Dept of Neurological Sciences
state: Nebraska
city: Las Vegas
country: United States
facility: Cleveland Clinic - Lou Ruvo Center for Brain Health
state: Nevada
city: New York
country: United States
facility: Columbia University - Taub Institute/Neurology Dept
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Dept of Neurology
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic - Center for Brain Health
state: Ohio
city: Columbus
country: United States
facility: Ohio State University - Dept of Neurology
state: Ohio
city: Portland
country: United States
facility: Center for Cognitive Health
state: Oregon
city: Houston
country: United States
facility: Houston Methodist Hospital - Stanley Appel Neurology Dept
state: Texas
city: Arlington
country: United States
facility: Sana Research
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University - Parkinson's and Movement Disorders Center
state: Virginia
city: Amsterdam
country: Netherlands
facility: Brain Research Center - Amsterdam
city: Den Bosch
country: Netherlands
facility: Brain Research Center - Den Bosch
city: Zwolle
country: Netherlands
facility: Brain Research Center - Zwolle
city: Belfast
country: United Kingdom
facility: Belfast Health & Social Care Trust
city: Cambridge
country: United Kingdom
facility: Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital - Windsor Research Unit
city: London
country: United Kingdom
facility: South London and Maudsley NHS Foundation Trust
city: London
country: United Kingdom
facility: Re:Cognition Health
city: London
country: United Kingdom
facility: University College London (UCL) Clinical Research Facility, University College London Hospitals NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Campus Ageing Research Unit (CARU) - Newcastle upon Tyne, CNTW NHS Foundation Trust
city: Redruth
country: United Kingdom
facility: Cornwall Partnership NHS Foundation Trust (University of Exeter)
city: Southampton
country: United Kingdom
facility: Memory Assessment and Research Centre (MARC) - Moorgreen Hospital
Study officials:
References: