An Open-label, Exploratory, Phase II, Proof-of Concept, Clinical Study to Assess the Safety and Tolerability of EI-1071 in Patients With Alzheimer's Disease (AD)

Elixiron Immunotherapeutics (Hong Kong) Ltd.2 sites in 1 country15 target enrollmentDecember 16, 2024

ConditionsMild, Moderate, or Severe Alzheimer's Disease

InterventionsEI-1071 tablet, oral

DrugsEI-1071 tablet, oral

Overview

Phase: Phase 2
Intervention: EI-1071 tablet, oral
Conditions: Mild, Moderate, or Severe Alzheimer's Disease
Sponsor: Elixiron Immunotherapeutics (Hong Kong) Ltd.
Enrollment: 15
Locations: 2
Primary Endpoint: Change from Baseline to Week 4 [¹⁸F] FEPPA Binding in Selected Brain Regions of Interest
Status: Recruiting
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

December 16, 2024

End Date

June 1, 2026

Last Updated

9 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Elixiron Immunotherapeutics (Hong Kong) Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Must meet all the clinical criteria for mild to severe AD (i.e., probable or possible AD dementia by NIA-AA criteria; must have objective evidence of cognitive impairment at Screening
•Clinical Dementia Rating Scale (CDR)≧0.5
•If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening.
•Adequate hematologic, hepatic, and renal function at the screening visit defined by the following criteria:
•Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
•Hemoglobin \[Hgb\] \> 10 g/dL
•Platelet count ≥ 100 × 10⁹/L
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1 × upper limit of normal (ULN)
•Total bilirubin and direct bilirubin ≤ 1.0 × ULN
•Alkaline phosphatase (ALP) ≤ 1.0 × ULN

Exclusion Criteria

•Body weight ≥ 150 kg or body mass index (BMI) ≥ 35 kg/m² at the screening visit.
•Prior use of pexidartinib (Turalio), other chemical entities, or any biologic treatment targeting colony stimulating factor 1 (CSF-1) or the CSF-1 receptor within 3-month of the first dose with EI-1071; previous uses of oral tyrosine kinase inhibitors are allowed (e.g., imatinib or nilotinib).
•AD patients with low binding affinity for tracer TSPO rs6971 SNP polymorphism at screening
•Pregnant, breast feeding or plan to be pregnant women during the study period
•Active tuberculosis (TB), active or chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) or known active or chronic infection with human immunodeficiency virus (HIV) at screening or in the medical history.
•Any medical or neurological/neurodegenerative condition (including mental deficit, intracranial tumor, glioma or meningioma; head trauma, Lewy body dementia; other disease than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns
•Clinically significant, unstable psychiatric illness or have contraindications to brain magnetic resonance imaging (MRI) or PET scans
•Have had a stroke or Transient Ischemic Attack (TIA), unexplained loss of consciousness or relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities in the past year based on medical history (with MRI imaging results as confirmation in the medical history) at screening. Subjects with clinically relevant cerebrovascular abnormalities in MRI will be excluded per PI's discretion.
•Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine (including poor-controlled T2DM), neurological, immunodeficiency, pulmonary, or other disorder or disease at the screening visit (such as neurological or cognitive impairment/decline due to substance abuse, vitamin B12 deficiency, abnormal thyroid function, or other underlying condition might contribute to cognitive, functional or behavioral impairment will be excluded) by investigator's judgment at screening; subjects who have to be fed by enteral tube will be excluded.
•History of or ongoing malignancy or carcinoma (either concurrent or within the last year of starting study treatment) that requires therapy (e.g., surgical, chemotherapy, or radiation therapy), except for adequately treated basal or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix or breast

Arms & Interventions

EI-1071 dose

Intervention: EI-1071 tablet, oral

Outcomes

Primary Outcomes

Change from Baseline to Week 4 [¹⁸F] FEPPA Binding in Selected Brain Regions of Interest

Time Frame: Baseline, Week 4

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

Secondary Outcomes

Number of Participants With at Least One Adverse Events (AEs) or Serious Adverse Events (SAEs) by CTCAE v5.0(From Day 1 up to Day 84)
Change From Baseline to Week 12 as Measured by CDR-SB(Baseline, Week 4, Week 12)
Mean Change From Baseline to Week 12 in Mini Mental State Exam (MMSE) Score(Baseline, Week 4, Week 12)
Change From Baseline to Week 12 in Alzheimer Disease Assessment Scale-Cognition Subscale 11 (ADAS-Cog11) Score(Baseline, Week 4, Week 12)
Change From Baseline to Week 12 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score(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(Baseline, Week 4, Week 12)
EI-1071 concentrations in plasma(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(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(Predose in Day 1 and 2-4 hours post dose in Day 28)
Physical Examination (PE)(Baseline, Day 1, Week 2, Week 4, Week 8, Week 12)
Vital Sign(Baseline, Day 1, week 2, week 4, week 8, week 12)
Electrocardiograms (ECGs) changes from baseline for PR(Baseline, Day 1, week 2, week 4, week 8, week 12)
Electrocardiograms (ECGs) changes from baseline for QRS duration(Baseline, Day 1, week 2, week 4, week 8, week 12)
Electrocardiograms (ECGs) changes from baseline in T wave(Baseline, Day 1, week 2, week 4, week 8, week 12)
Electrocardiograms (ECGs) changes from baseline in QTc(Baseline, Day 1, week 2, week 4, week 8, week 12)