Clinical trial NCT05413655: A Study of Oral EX039 in Subjects with Mild Alzheimer's Disease
Official title: A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Oral EX039 As Add-on to Acetylcholine Esterase Inhibitors in Subjects with Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Excelsior
Sponsor class: INDUSTRY
Collaborators: name: Formosa Biomedical Technology Corp.
First posted: 2022-06-10
Enrollment: 120
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 2, randomized, double-blind, placebo-controlled study of oral EX039 as add-on to Acetylcholine Esterase Inhibitors in subjects with mild Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

* Aged 50-80 years.
* Clinical diagnosis of probable mild Alzheimer disease dementia based on National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA criteria, 2011)
* Last time (which must be within 3 months ) of Mini Mental State Exam (MMSE) between 10-26.
* Last time (which must be within 3 months) of Clinical Dementia Rating (CDR) score of 1.
* Physically healthy and all laboratory assessments (including hematology, chemistry, urinalysis and electrocardiograph) are within normal range or meet the following criteria:

  * AST, ALT level ≦ upper limit of normal
  * Creatine Kinase (CK) concentration more than 3 times upper limit of normal
  * Serum creatinine level ≦ upper limit of normal
  * HbA1c more than 8.0
* Complaints of subjective memory impairment and cognitive disturbances by patients themselves or caregivers, including memory loss and at least one of the following cognitive disturbances: language, perceptual skills, attention, constructive abilities, orientation, problem solving, functional abilities.
* Cognitive deficits caused impairment in social or occupational function.
* Disease progression with gradual and continued decline from a previous level of functioning.
* Female subjects must be of non-childbearing potential (greater than 1 year without menstrual period in the absence of hormone replacement therapy) or surgically sterile. If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test and must not be lactating at screening visit. Female subjects of childbearing potential and who are sexually active are required to practice adequate methods of birth control. Male subjects who are sexually active will also be required to use an adequate form of birth control.
* Has sufficient education equivalent to elementary education to communicate effectively and were capable of completing the assessments of the study.

Exclusion Criteria:

* Having other causes of dementia.
* Having substantial concomitant cerebrovascular disease (defined by a history of a stroke

  / intracranial hemorrhage temporally related to the onset of worsening of cognitive impairment) per investigator judgement.
* Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
* Medical history or diagnosis of any of the following symptomatic and unstable / uncontrolled conditions per investigator's judgement:

  * Uncontrolled cardiovascular illnesses such as chronic congestive heart failure (with or without edema), tachycardia, arrhythmias, uncontrolled hypertension.
  * Significant ischemic heart disease, myocardial infarction within the last two years and/or with residual angina, orthopnea, conduction defects (ECG), or any other clinical significant heart disease classified as New York Heart Association (NYHA) III or IV.
  * Significant gastrointestinal disorders (for example gastrointestinal bleeding within the last two years, malabsorption syndromes, post-gastrectomy, or active peptic ulcer disease).
  * Uncontrolled endocrine disease such as uncontrolled diabetes mellitus or hyperthyroidism.
  * Unstable/Uncontrolled major depression.
  * Has neurological disease (other than dementia of Alzheimer's type, such as: Lewy body dementia - primary diagnosis, Huntington's disease, Parkinson's Disease, encephalitis, epilepsy, vascular or multiinfarct dementia, stroke, congenital mental deficiency, multiple sclerosis).
  * Significant pulmonary disease predisposing to hypoxia.
  * Has major physical illnesses (e.g. brain tumor, craniocerebral trauma, thyroid disease)
* Any other psychiatric disorders such as schizophrenia, or mental retardation.
* Any suicidal actions in the past 2 years (per investigator judgement i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).
* Hachinski Ischemic Score \> 4
* Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic and Statistical Manual of Mental Disorders \[DSM-V\] or in the opinion of the investigator)
* Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed.
* Has other condition(s) that in the opinions of investigators to be ineligible to participate in this study, e.g. Subject who cannot swallow the capsule whole.

Primary outcomes:
measure: Change in Alzheimer's Disease Assessment Scale-cognitive
timeFrame: Week 28
measure: Change in Clinical Dementia Rating-Sum of Boxes
timeFrame: Week 28
Secondary outcomes:
measure: Change in Clinician's Interview-Based Impression of Change Plus Caregiver Input
timeFrame: Week 4, 12, 20, 28
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Week 30
measure: Responder rate assessment
timeFrame: Week 28
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Kaohsiung Medical University
name: Ching-Kuan Liu, Dr.
role: PRINCIPAL_INVESTIGATOR
References: