A Study of ATH-1017 in Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This study is designed to evaluate treatment effects of ATH-1017 (fosgonimeton) in mild to moderate Alzheimer's subjects with a randomized treatment duration of 26-weeks.

Detailed Description
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This study is designed to assess the correlation of the functional translational biomarker P300 latency and change in ADAS-Cog11 induced by ATH-1017 therapy, over 26-week randomized, double-blind treatment.

Official Title
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A Randomized, Placebo-Controlled, Translational Study of ATH-1017 in Subjects With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease, Dementia of Alzheimer Type

Intervention / Treatment
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* Drug: ATH-1017
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 55 to 85 years Mild-to-moderate AD dementia subjects, MMSE 14-24, CDR 1 or 2 at Screening Clinical diagnosis of dementia, due probably to AD, by Revised National Institute on Aging-Alzheimer's Association criteria (McKhann, 2011) Reliable and capable support person/caregiver Treatment-free or receiving stable acetylcholinesterase inhibitor (AChEI) treatment, defined as: Treatment-naïve, OR Subjects are on a stable, approved dose of an AChEI (except for donepezil at 23 mg PO) for at least 3 months before Screening OR Subjects who received an AChEI in the past and discontinued 4 weeks prior to Screening Key Exclusion Criteria: History of significant neurologic disease, other than AD, that may affect cognition, or concurrent with the onset of dementia History of unexplained loss of consciousness, and epileptic fits (unless febrile) Subject has atypical variant presentation of AD, if known from medical history, particularly non-amnestic AD History of brain MRI scan indicative of any other significant abnormality Hearing test result considered unacceptable for auditory ERP P300 assessment Diagnosis of severe major depressive disorder even without psychotic features Significant suicide risk History within 2 years of Screening, or current diagnosis of psychosis Myocardial infarction or unstable angina within the last 6 months Clinically significant (in the judgment of the investigator) cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable) Subject has either hypertension (supine diastolic blood pressure > 95 mmHg), or symptomatic hypotension in the judgment of the investigator Clinically significant ECG abnormality at Screening Renal insufficiency (serum creatinine > 2.0 mg/dL) Hepatic impairment with alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of normal, or Child-Pugh class B and C Malignant tumor within 3 years before Screening Memantine in any form, combination or dosage within 4 weeks prior to Screening Donepezil at 23 mg PO The subject has received active amyloid or tau immunization (i.e., vaccination for Alzheimer's disease) at any time, or passive immunization (i.e., monoclonal antibodies for Alzheimer's disease) within 6 months of Screening

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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No

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
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel-group study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>Daily subcutaneous (SC) injection of Low Dose ATH-1017 | Drug: ATH-1017<br>* Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe<br>|
| Experimental: High Dose<br>Daily subcutaneous (SC) injection of High Dose ATH-1017 | Drug: ATH-1017<br>* Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe<br>|
| Placebo Comparator: Placebo<br>Daily subcutaneous (SC) injection of Placebo | Drug: Placebo<br>* Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-related Potential (ERP) P300 Latency at Baseline | ERP P300 was a method of recording brain activity elicited by external stimuli, for example (e.g.), an oddball auditory stimulus, particularly of working memory access. The participant had to perform a task related to auditory stimuli in order to assess the P300 component (latency). The stimulus consisted of an oddball paradigm with 2 sound stimuli. Stimuli were presented through headphones and auditory stimulation for P300 was assessed in a recording lasting up to 10 minutes. It was calculated as the average across the pre-dose values at Baseline visit. Baseline was defined as Day 1. | At Baseline (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Baseline | The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. It was performed to evaluate the correlation of ERP P300 latency and cognition. 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. Baseline was defined as Day 1. | At Baseline (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Cognition, Dementia, ATH-1017, Memory Loss