An open-label, exploratory, phase II, proof-of concept, clinical study to assess the safety and tolerability of EI-1071 and the effects of EI-1071 on neuroinflammation in patients with mild, moderate, or severe Alzheimer's disease
This is an open-label, phase II, exploratory, proof-of-concept study to assess the safety and tolerability of EI-1071 and the effects of EI-1071 on neuroinflammation in patients with mild, moderate, or sever Alzheimer's disease (AD). The main goals include: 1. to validate mechanism-engagement of EI-1071 by tracing the change of activated microglia in selected brain regions in AD patients using TSPO PET/MRI imaging. 2. to assess effects of EI-1071 on changes of inflammatory biomarkers associated with AD progression.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Dose: 448.2 mg BID for 28 days
Taipei Veterans General Hospital
Taipei, Taiwan
RECRUITINGTri-Service General Hospital
Taipei, Taiwan
NOT_YET_RECRUITINGChange from Baseline to Week 4 [¹⁸F] FEPPA Binding in Selected Brain Regions of Interest
Change from baseline in volume of distribution (Vt) of \[¹⁸F\]FEPPA binding in selected brain regions of interest in each \[¹⁸F\]FEPPA Positron Emission Tomography (PET) scan obtained from individual patient after 28 days of EI-1071 repeated dosing
Time frame: Baseline, Week 4
Number of Participants With at Least One Adverse Events (AEs) or Serious Adverse Events (SAEs) by CTCAE v5.0
An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: From Day 1 up to Day 84
Change From Baseline to Week 12 as Measured by CDR-SB
CDR was derived through semi-structured interview with the participant and an appropriate informant, and it rated impairment across six domains: memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care on a 5-point scale for which 0=no impairment, 0.5=questionable impairment, and 1, 2, and 3=mild, moderate, and severe impairment, respectively. The CDR-SB is based on
Time frame: Baseline, Week 4, Week 12
Mean Change From Baseline to Week 12 in Mini Mental State Exam (MMSE) Score
MMSE is a rater-administered performance-based outcome (PerfO) that includes a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target six areas: orientation, registration, attention, short-term recall, language, and constructional praxis/visuospatial abilities. Total score ranges from 0-30, with lower scores indicating greater impairment. A positive change from baseline indicates improvement.
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Time frame: Baseline, Week 4, Week 12
Change From Baseline to Week 12 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score
The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. The standard 11 items (and corresponding score range) were: word recall (0-10), commands (0-5), constructional praxis (0-5), naming objects and fingers (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), spoken language ability (0-5), comprehension of spoken language (0-5), word-finding difficulty (0-5), and remembering test instructions (0-5). The test included 7 performance items and 4 clinician-rated items. The ADAS-Cog11 total score was the sum of all 11 individual items, with a total score ranging from 0 (no impairment) to 70 (severe impairment). Higher scores indicated more severe cognitive impairment. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 4, Week 12
Change From Baseline to Week 12 in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score
ADCS-ADL is a 23-item rater-administered, observer-reported outcome (ObsRO) that captures a participant's ability to perform basic activities of daily living (e.g., eating and toileting) and more complex ADL or instrumental activities of daily living (iADL, e.g., using the telephone, managing finances, preparing a meal). Total score ranges from 0-78, with higher scores reflecting better functioning. A positive change from baseline indicates improvement.
Time frame: Baseline, Week 4, Week 12
Change From Baseline to Week 12 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score
The NPI-Q evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavioral disturbances and appetite/eating abnormalities. The severity of each neuropsychiatric symptom is rated on a 3-point scale (mild, moderate and marked). The total severity score range is from 0 to 36 with higher scores representing higher severity.
Time frame: Baseline, Week 4, Week 12
EI-1071 concentrations in plasma
EI-1071 concentrations in plasma samples will be assessed.
Time frame: Predose and 2-3 hours post dose in Day1 and Day 14, predose and 2-4 hours post dose in Day 28
EI-1071 concentrations in cerebrospinal fluid
EI-1071 concentrations in cerebrospinal fluid samples will be assessed.
Time frame: Predose in Day 1 and 2-4 hours post dosing in Week 4
Neuroinflammation and/or neurodegeneration biomarkers levels in plasma and in cerebrospinal fluid
Neuroinflammation and/or neurodegeneration biomarkers levels in plasma or in cerebrospinal fluid will be assessed.
Time frame: Predose in Day 1 and 2-4 hours post dose in Day 28
Physical Examination (PE)
Clinically significant abnormal changes in physical examinations
Time frame: Baseline, Day 1, Week 2, Week 4, Week 8, Week 12
Vital Sign
Clinically significant abnormal changes in vital signs
Time frame: Baseline, Day 1, week 2, week 4, week 8, week 12
Electrocardiograms (ECGs) changes from baseline for PR
Clinically significant abnormal changes from baseline in ECG for PR
Time frame: Baseline, Day 1, week 2, week 4, week 8, week 12
Electrocardiograms (ECGs) changes from baseline for QRS duration
Clinically significant abnormal changes from baseline in ECGs for QRS duration
Time frame: Baseline, Day 1, week 2, week 4, week 8, week 12
Electrocardiograms (ECGs) changes from baseline in T wave
Clinically significant abnormal changes from baseline in ECGs in T wave
Time frame: Baseline, Day 1, week 2, week 4, week 8, week 12
Electrocardiograms (ECGs) changes from baseline in QTc
Clinically significant abnormal changes from baseline in ECGs in corrected QT interval (QTc)
Time frame: Baseline, Day 1, week 2, week 4, week 8, week 12