Clinical Study of Neflamapimod in Patients With Dementia With Lewy Bodies
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|ClinicalTrials.gov Identifier: NCT05869669|
Recruitment Status : Recruiting
First Posted : May 22, 2023
Last Update Posted : September 22, 2023
|Condition or disease||Intervention/treatment||Phase|
|Dementia With Lewy Bodies||Drug: Neflamapimod Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Phase 2b (hypothesis-testing), multi-center, randomized, double-blind, placebo-controlled study|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients With Dementia With Lewy Bodies|
|Actual Study Start Date :||May 1, 2023|
|Estimated Primary Completion Date :||August 2024|
|Estimated Study Completion Date :||March 2025|
Active Comparator: Neflamapimod
Neflamapimod will be administered with food for 16 weeks in subjects with DLB. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).
Neflamapimod is a highly specific inhibitor of the intra-cellular enzyme mitogen-activated protein kinase14 (p38α) provided in 40mg capsules
Other Name: VX-745
Placebo Comparator: Placebo
Placebo will be administered with food for 16 weeks in subjects with DLB. Subjects will receive 3 capsules per day (TID) with food (i.e., with the morning, mid-day and evening meals).
Placebo is a capsule that looks just like neflamapimod but without the active ingredients
- Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) in neflamapimod-treated subjects compared to placebo recipients. [ Time Frame: 16 weeks ]
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.
- Change in Timed Up and Go Test (TUG) in neflamapimod-treated subjects compared to placebo recipients. [ Time Frame: 16 weeks ]
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.
- 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. [ Time Frame: 16 weeks ]
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), Letter Fluency Test (LFT).
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.
- Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-GCIC) score at Week 16 in neflamapimod-treated subjects compared to placebo recipients. [ Time Frame: 16 weeks ]
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.
- Exploratory outcome - Dementia Cognitive Fluctuations Scale (DCFS) [ Time Frame: 16 weeks ]
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.
- Exploratory outcome - 12-item Neuropsychiatric Inventory (NPI-12) [ Time Frame: 16 weeks ]
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.
- Exploratory outcome - Movement Disorder Society - Unified Parkinson's Disease Rating Scale - Part III (MSD-UPDRS3) motor examination (Part III) [ Time Frame: 16 weeks ]
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.
- Exploratory outcome - EEG [ Time Frame: 16 weeks ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05869669
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