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

A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment in Subjects With Mild to Moderate Alzheimer's Disease

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.

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.

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