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Dementia With Lewy Bodies (DLB)Phase 2AscenD-LBNCT04001517

Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies

A Phase 2 study testing Neflamapimod in people with Dementia With Lewy Bodies (DLB), run by EIP Pharma Inc at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Dementia With Lewy Bodies (DLB)
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
91 participants
Where
24 sitesin 2 countries
Study dates
30 Sep 2019to 30 Jun 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and women aged ≥55 years.
  • Subject or subject's legally authorized representative is willing and able to provide written informed consent.
  • Probable DLB and identified cognitive deficits, according to current consensus criteria (McKeith et al, 2017), specifically one core clinical feature and a positive DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the subject would also qualify.
  • MMSE score of 15-28, inclusive, during Screening.
  • Currently receiving cholinesterase inhibitor therapy, having 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.
  • Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
  • No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
  • Must have reliable informant or caregiver.

Who cannot join

  • 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).
  • 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.
  • 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.
  • Diagnosis of alcohol or drug abuse within the previous 2 years.
  • 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.
  • 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.
Show all 11Show fewer
  • Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
  • Participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
  • History of previous neurosurgery to the brain.
  • If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
  • 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.

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States22 sites

  • University of Michigan

    Ann Arbor, Michigan, 48105

  • University of Colorado

    Aurora, Colorado, 80045

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Massachusetts General Hospital

    Charlestown, Massachusetts, 02129

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The Ohio State University

    Columbus, Ohio, 43210

  • University of Kansas Medical Center

    Kansas City, Kansas, 66103

  • University of California San Diego (UCSD)

    La Jolla, California, 92037

  • Cleveland Clinic - Lou Ruvo Center for Brain Health

    Las Vegas, Nevada, 89106

  • Elite Clinical Research

    Miami, Florida, 33144

  • New York Presbyterian Hospital - Columbia University Medical Center

    New York, New York, 10032

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Summit Research Network

    Portland, Oregon, 97210

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • National Clinical Research, Inc.

    Richmond, Virginia, 23294

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14618

  • Pacific Neuroscience Institute

    Santa Monica, California, 90404

  • University of Washington

    Seattle, Washington, 98104

  • Inland Northwest Research

    Spokane, Washington, 99202

Other trials in United States

Netherlands2 sites

  • Brain Research Center

    's-Hertogenbosch

  • Brain Research Center

    Amsterdam

Other trials in Netherlands

About this study

Official title: A Double-Blind, Placebo-Controlled 16-Week Study of the Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (DLB)

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. The primary objective is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as a potential biomarker for DLB.

Being tested
Neflamapimod
Medical subject headings
Lewy Body Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NeflamapimodDrug

    Double-Blind, Placebo-Controlled

Study groups in NCT04001517
Study groupRoleWhat they receive
NeflamapimodExperimental40 mg capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg
Receives: Drug: Neflamapimod
PlaceboPlacebo comparator40 mg matching placebo capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg
Receives: Drug: Neflamapimod

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test

    Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was 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 indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.

    Measured: As the analysis was by Mixed Model for Repeated Measures, all time points at which NTB was assessed utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

Secondary outcomes (6)

  1. Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)

    Change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score from Baseline to Week 8 and Week 16 based on semi-quantitative scoring of six domains (i.e., "box": 1) memory, 2) orientation, 3) judgement \& reasoning, 4) home \& hobbies, 5) community affairs, and 6) personal care. The CDR score ranges from 0 (no impairment), 0.5 (questionable impairment), 1 (mild impairment), 2 (moderate impairment), and 3 (severe impairment). The domain (box) scores are then added for a Sum of Boxes score. With six domains, the CDR-SB score then ranges from 0 to 18; with higher scores indicated worse outcomes.

    Measured: As the analysis was by Mixed Model for Repeated Measures, both time points at which CDR-SB was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

  2. Mini-Mental State Examination (MMSE)

    The Mini-Mental State Examination (MMSE) is a general measure of cognition that assesses orientation, memory, concentration, language, and praxis. Scores range from 0 to 30 with lower scores indicating greater cognitive impairment, i.e. a worse outcome). The MMSE was assessed at Week 8 and Week 16 during the study.

    Measured: As the analysis was by Mixed Model for Repeated Measures, both time points at which MMSE was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

  3. Neuropsychiatric Inventory (NPI-10) - Mean Change in Hallucinations Domain Score

    The NPI-10 consists evaluates ten domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor activity. If caregiver reports symptoms within a domain then the caregiver rates the frequency of the symptoms on a 4-point scale, and severity on a 3-point scale. Total score for each domain is the frequency score multiplied by the severity score; i.e. the domain score (e.g. for hallucinations) for any one domain ranges from 0-12, with higher scores indicating worsening. A secondary objective of this study was to evaluate the effect of neflamapimod in four specific domains, specifically depression (dysphoria), anxiety, hallucinations, and agitation/aggression, in neflamapimod-treated subjects compared to placebo-recipients. Of these four, the only domain in which more than one-quarter of the patients reported symptoms is hallucinations, and the result of this analysis is reported.

    Measured: As the analysis was by Mixed Model for Repeated Measures, all time points at which NPI-10 was assessed (weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

  4. International Shopping List Test (ISLT) - Immediate Recall

    The International Shopping List Test (ISLT) was developed specifically to assess verbal list learning and memory in people from different language and cultural backgrounds. 12 words, consisting to items typically in a grocery shopping list in the specific culture are provided verbally, and subject asked to recall ask many words as possible. The immediate recall score consists of the number of words that the subject correctly repeats during three consecutive trials immediately following provision of words. The range is then from 0 to 36 (12 words maximum in each of 3 trials), with higher scores (i.e., the more words recalled) reflecting better outcomes.

    Measured: As the analysis was by Mixed Model for Repeated Measures, both time points at which ISLT was assessed (Weeks 4, 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

  5. Timed Up and Go Test (TUG)

    The Timed Up and Go test assesses function mobility, and was included in the study to evaluate the effects of neflamapimod on motor function. The TUG measures the time in seconds that a person takes to rise from a chair, walk three meters, turn around 180 degrees, walk back to the chair, and sit down while turning 180 degrees. The TUG was evaluated at Baseline, and Weeks 8 and 16 of the study. There is no minimum or maximum value for this test, though in Parkinson's disease patients values above 11.5 seconds was associated with an increased risk of falls and each one second increase in the time required to complete the TUG is associated with a 5.4% increase in the risk of falls (Arch Phys Med Rehabil. 2013;94: 1300-1305). That is, an increase in the time required to complete the TUG is a worse outcome.

    Measured: As the analysis was by Mixed Model for Repeated Measures, both time points at which the TUG was assessed (week 8 and 16) was utilized in the analysis. The difference reported is the mean difference over the entire course of the study.

  6. Quantitative Electroencephalogram (qEEG)m - Dominant Peak Frequency Over Parietal Lobe

    Change in quantitative electroencephalogram (qEEG) parameters with the subject awake in accordance with the 10-20 International System of Electrode placement was to be evaluated as a potential biomarker for DLB. However, due to COVID19 related restrictions, baseline and week 16 EEG recordings were obtained only in limited number of subjects. As slowing of the dominant frequency band by qEEG over posterior aspects of the brain has been recognized to be prominent in DLB, the change in the dominant frequency band over the parietal lobe in Hz from baseline to week 16 is reported. This is a continuous variable with no minimum or maximum. A decrease in the frequency (i.e., slowing) reflects worsening of disease, while a positive treatment effect would be an increase in the frequency. With the limited number of subjects formal statistical analysis was not conducted.

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2019
  2. Study start30 Sep 2019
  3. Primary completion30 Jun 2020
  4. Study completion30 Jun 2020

Resources

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
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04001517
Sponsor's protocol ID
EIP19-NFD-501
Acronym
AscenD-LB
Status last verified
Jun 2023
First submitted
7 Jun 2019
Last updated
29 Jun 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Prins ND, de Haan W, Gardner A, Blackburn K, Chu HM, Galvin JE, Alam JJ. Phase 2A Learnings Incorporated into RewinD-LB, a Phase 2B Clinical Trial of Neflamapimod in Dementia with Lewy Bodies. J Prev Alzheimers Dis. 2024;11(3):549-557. doi: 10.14283/jpad.2024.36.

    PubMed 38706271

  • Alam JJ, Maruff P, Doctrow SR, Chu HM, Conway J, Gomperts SN, Teunissen C. Association of Plasma Phosphorylated Tau With the Response to Neflamapimod Treatment in Patients With Dementia With Lewy Bodies. Neurology. 2023 Oct 24;101(17):e1708-e1717. doi: 10.1212/WNL.0000000000207755. Epub 2023 Sep 1.

    PubMed 37657939

  • Jiang Y, Alam JJ, Gomperts SN, Maruff P, Lemstra AW, Germann UA, Stavrides PH, Darji S, Malampati S, Peddy J, Bleiwas C, Pawlik M, Pensalfini A, Yang DS, Subbanna S, Basavarajappa BS, Smiley JF, Gardner A, Blackburn K, Chu HM, Prins ND, Teunissen CE, Harrison JE, Scheltens P, Nixon RA. Preclinical and randomized clinical evaluation of the p38alpha kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration. Nat Commun. 2022 Sep 21;13(1):5308. doi: 10.1038/s41467-022-32944-3.

    PubMed 36130946

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neflamapimod in people with Dementia With Lewy Bodies (DLB), run by EIP Pharma Inc at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Z-score of a Study-specific Neuropsychological Test Battery (NTB) Including Tests From Cogstate Battery, Letter Fluency Test and Category Fluency Test (time frame: As the analysis was by Mixed Model for Repeated Measures, all time points at which NTB was assessed utilized in the analysis. The difference reported is the mean difference over the entire course of the study.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04001517, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2023.

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