ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease

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

Detailed Description
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The study is designed to evaluate safety and efficacy of ATH-1017 in mild to moderate AD subjects, with randomized, parallel-arm treatment duration of 26 weeks, and based on clinical diagnostic criteria of Alzheimer's disease. Clinical efficacy is demonstrated by improvement in cognition and global/functional assessments comparing treatment to placebo.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment 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) Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m2 at Screening Reliable and capable support person/caregiver Treatment-free (subjects not receiving acetylcholinesterase inhibitor [AChEI] treatment), defined as: Treatment-naïve, OR Subjects who received an AChEI in the past and discontinued at least 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 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 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 cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable) Subject has either hypertension or symptomatic hypotension Clinically significant ECG abnormality at Screening Chronic kidney disease with estimated glomerular filtration rate (eGFR) <45 mL/min 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 Acetylcholinesterase inhibitors in any dosage form 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: Dosage<br>Daily subcutaneous (SC) injection of 40mg 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 |
| --- | --- | --- |
| To evaluate the clinical efficacy of ATH1017 in subjects not on background acetylcholinesterase inhibitors (AChEIs) | The Global Statistical Test (GST) score that combines the change from baseline scores from cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11]) and function (Alzheimer's Disease Cooperative Study-Activities of Daily Living, 23-item version [ADCS-ADL23] score) | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition | Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11] (Range of 0 to 70, where 0 is least impairment and 70 is most severe impairment) | Week 26 | 
| Activities of Daily Living | Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23] (Range of 0 to 78, where a higher score indicates greater function) | Week 26 | 
| To determine the effect of ATH1017 on plasma neurofilament light chain (NfL) concentration | NfL concentration change from Baseline at Week 26 | Week 26 | 

 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, LIFT AD, Fosgonimeton