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

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

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.

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.

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