RewinD-LB - Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies

Dementia With Lewy Bodies Clinical Trial

Official title:

A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05869669
• Other study ID #: EIP21-NFD-504
• Secondary ID: R01AG0805362023-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 1, 2023
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: EIP Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: March 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Dementia
• Dementia With Lewy Bodies
• Lewy Body Disease

Intervention

Drug:
• Neflamapimod
Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38a) provided in 40mg capsules
• Placebo
Placebo is a capsule that looks just like neflamapimod but without the active ingredients

Locations

Country	Name	City	State
Netherlands	Brain Research Center - Amsterdam	Amsterdam
Netherlands	Brain Research Center - Den Bosch	Den Bosch
Netherlands	Brain Research Center - Zwolle	Zwolle
United Kingdom	Belfast Health & Social Care Trust	Belfast
United Kingdom	Cambridgeshire and Peterborough NHS Foundation Trust, Fulbourn Hospital - Windsor Research Unit	Cambridge
United Kingdom	Re:Cognition Health	London
United Kingdom	South London and Maudsley NHS Foundation Trust	London
United Kingdom	University College London (UCL) Clinical Research Facility, University College London Hospitals NHS Foundation Trust	London
United Kingdom	Campus Ageing Research Unit (CARU) - Newcastle upon Tyne, CNTW NHS Foundation Trust	Newcastle Upon Tyne
United Kingdom	Cornwall Partnership NHS Foundation Trust (University of Exeter)	Redruth
United Kingdom	Memory Assessment and Research Centre (MARC) - Moorgreen Hospital	Southampton
United States	Sana Research	Arlington	Virginia
United States	University of Colorado - Dept of Neurology	Aurora	Colorado
United States	Johns Hopkins School of Medicine - Dept of Neurology	Baltimore	Maryland
United States	University of Miami - Dept of Neurology Comprehensive Center for Brain Health	Boca Raton	Florida
United States	NeuroScience Research Center	Canton	Ohio
United States	University of North Carolina - Dept of Neurology	Chapel Hill	North Carolina
United States	Mass General Hospital/Harvard Medical School - Dept of Neurology	Charlestown	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic - Center for Brain Health	Cleveland	Ohio
United States	Ohio State University - Dept of Neurology	Columbus	Ohio
United States	Re:Cognition Health - Fairfax	Fairfax	Virginia
United States	Houston Methodist Hospital - Stanley Appel Neurology Dept	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCSD Health Sciences - Movement Disorders Center	La Jolla	California
United States	JEM Research Institute	Lake Worth	Florida
United States	Cleveland Clinic - Lou Ruvo Center for Brain Health	Las Vegas	Nevada
United States	Tandem Clinical Research	Marrero	Louisiana
United States	ClinCloud	Melbourne	Florida
United States	Columbia University - Taub Institute/Neurology Dept	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	University of Nebraska Medical Center - Dept of Neurological Sciences	Omaha	Nebraska
United States	AdventHealth Neuroscience Research	Orlando	Florida
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	SC3 Research Group	Pasadena	California
United States	Panhandle Research and Medical Clinic	Pensacola	Florida
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Center for Cognitive Health	Portland	Oregon
United States	Virginia Commonwealth University - Parkinson's and Movement Disorders Center	Richmond	Virginia
United States	Mayo Clinic - Alzheimer's Disease Research Center	Rochester	Minnesota
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Banner Alzheimer's Institute - Edson Family Lewy Body Dementia Center	Tucson	Arizona
United States	Georgetown Univ Hospital - Dept of Neurology	Washington	District of Columbia

Sponsors (4)

Lead Sponsor	Collaborator
EIP Pharma Inc	CervoMed, Inc, National Institute on Aging (NIA), Worldwide Clinical Trials

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcome - Dementia Cognitive Fluctuations Scale (DCFS)	Change in DCFS score in neflamapimod-treated subjects compared to placebo recipients.; DCFS scores range from 4 to 20 where a higher score indicates more severe cognitive fluctuations and disease worsening.	16 weeks
Other	Exploratory outcome - 12-item Neuropsychiatric Inventory (NPI-12)	Change in neflamapimod-treated subjects compared to placebo recipients in the following: Select domains of the NPI-12, including depression (dysphoria), apathy, hallucinations, and agitation/aggression.; Change in hallucinations frequency x severity score within the NPI-12 in subjects who report hallucinations at baseline.; Change in sleep and night-time behavior change within the NPI-12.; NPI-12 scores range from 0 to 12 for each individual domain and 0 to 144 total score, where a higher score indicates worsening of neuropsychiatric symptoms.	16 weeks
Other	Exploratory outcome - Movement Disorder Society - Unified Parkinson's Disease Rating Scale - Part III (MSD-UPDRS3) motor examination (Part III)	Change in MDS-UPDRS3 score in neflamapimod-treated subjects compared to placebo recipients..; MDS-UPDRS 3 scores range from 0 to 108 where a higher score indicates more severe motor symptoms.	16 weeks
Other	Exploratory outcome - EEG	Change in beta functional connectivity and in alpha reactivity on quantitative EEG in neflamapimod-treated subjects compared to placebo recipients..; Functional connectivity will be analyzed as Amplitude Envelope Correlation (AECc), a measure of interregional communication within the brain. AECcs are computed by correlating the amplitude (energy) envelopes of oscillatory brain signals in two different brain regions. AECc ranges between 0 and 1, with higher AECc values indicating increased functional connectivity. In this study, the primary EEG evaluation will be AECc within the beta band (13-30 Hz), i.e. beta functional connectivity.	16 weeks
Primary	Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients.	The primary objective is to demonstrate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the CDR-SB scale.; CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.	16 weeks
Secondary	Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients.	Demonstrate that neflamapimod improves motor function in patients with DLB, compared to placebo, as assessed by the TUG test.; TUG scores typically range from 6 to 20 seconds with a higher score indicating worse mobility. A score of >15 indicates an increased risk of falls.	16 weeks
Secondary	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.	Demonstrate that neflamapimod improves cognition, compared to placebo, as assessed by a DLB-specific NTB in patients with DLB. NTB includes Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB).; Each score on the individual tests is converted to a z-score, and then a total z-score for the composite is calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicates an improvement in cognition and a negative change in z-score indicates a worsening in cognition.	16 weeks
Secondary	Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients.	Demonstrate that neflamapimod improves global (cognition, function and behavior) disease status evaluated by a clinician with caregiver input, compared to placebo, in patients with DLB, as assessed ADCS-CGIC score.; ADCS-CGIC scores range from 1 to 7, where 1 = marked improvement, 2= moderate improvement, 3 = minimal improvement, 4 = no change, 5 = minimal worsening, 6 = moderate worsening, and 7 = marked worsening.	16 weeks