Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment

Study Overview
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Brief Summary
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The purpose of this study is to find out if different doses of Investigational Drug are safe, tolerable, and if they have an effect on Mild Cognitive Impairment (MCI).

Detailed Description
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Pre-Clinical experiments indicate the AL-108 compound has neuroprotective, cognitive protective and neurotrophic properties; therefore, the compound could be tested in a variety of human diseases. Human diseases include Cognitive impairment associated with aging or neurodegenerative diseases such as Alzheimer's Disease. This clinical trial aims at providing the dose rationale as well as safety and tolerability information for AL-108 as evaluated after 12 weeks of intranasal administration in subjects with Mild Cognitive Impairment (MCI). There are currently no drugs approved for the treatment of MCI nor accepted treatment or standard treatment approach.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Effect on Cognitive Function of AL-108 After 12 Weeks of Intranasal Administration in Subjects With Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment, So Stated

Intervention / Treatment
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* Drug: AL-108
* Drug: AL-108
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female, at 55-85 years of age (inclusive) at screening Self-reported memory complaint, corroborated by spouse or companion as appropriate. Wechsler Memory Scale III (WMS-III) age-adjusted Logical Memory II score ≤ 5. Mini-Mental State Exam (MMSE) ≥24. Center for Epidemiologic Studies-Depression (CES-D) score <27. Normal thyroid function, defined as TSH, T3 and T4 within normal limits. Agree not to consume alcoholic beverages within 8 hours of each study visit. Willing and able to sign informed consent and complete the CTB and all other tests and procedures as listed in the protocol. Fluently reads and speaks English. Female subjects must be surgically sterile or post-menopausal for at least 2 years. If <2 years post-menopausal, then a follicle stimulating hormone (FSH) ≥40 mIU/mL must be obtained. Exclusion Criteria: Subjects who have any significant, untreated psychiatric illness or any CNS condition (such as schizophrenia, Parkinson's disease, stroke, etc.) that could interfere with the study evaluations or procedures or which poses an additional risk. Subjects with a history of uncomplicated depression may participate if in remission and on a stable dose of antidepressant medication for at least 2 months. History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities. History of alcohol or substance abuse or dependence within the past year. Acute infective sinusitis. History or presence of an abnormality of the external or internal structures of the nose or nasopharynx, except for surgical correction of the nasal septum or a broken nose at least 2 years previously, or surgical repair of cleft palate when <30 years of age. Use of medications that are known to cause frank obtundation of cognition Use of any approved or investigational medication for Alzheimer's Disease within 3 months of screening History of or current significant systemic disease judged to interfere with the study evaluations or likely to be a safety concern. Untreated sleep apnea or treatment for sleep apnea for <3 months. Abnormal clinical laboratory test results, specifically: Alanine transaminase (ALT) or aspartate transaminase (AST) >2 х the upper limit of normal (ULN),Hematology <80% the lower limit of normal, Creatinine ≥2 mg/dL and ,Other clinical laboratory values or vital signs considered clinically significant in the opinion of the Investigator. Treatment with any investigational drug, biologic, or device within the previous 30 days prior to screening. Surgery involving general anesthesia within the past 3 months or planned surgery requiring general anesthesia during the study period.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AL-108 5 mg<br>5 mg QD | Drug: AL-108<br>* 5 mg QD<br>|
| Active Comparator: AL-108 15 mg<br>15 mg BID | Drug: AL-108<br>* 15 mg BID<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 12 on the Composite Memory Variable |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Composite Memory Variable from baseline to weeks 4, 8, and 16 |  | 16 weeks | 
| Changes in test battery individual items from baseline to endpoints (weeks 4, 8, 12, and 16). |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Memory, Alzheimers, Cognition, Mind, Aging