A Study of ATH-1017 in Mild to Moderate Alzheimer's Disease (ACT-AD)

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease; Dementia of Alzheimer Type
• Intervention / Treatment: Drug: ATH-1017; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Central Coast, New South Wales, Australia, 2261
      • Central Coast Neurosciences Research
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Centre for Applied Medical Research, Translational Research Centre
    • Greenwich, New South Wales, Australia, 2065
      • HammondCare Greenwich Hospital
    • Macquarie Park, New South Wales, Australia, 2113
      • KaRa MINDS
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • HammondCare
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Organization
• United States
  • California
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany
  • Oregon
    • Portland, Oregon, United States, 97225
      • Center for Cognitive Health
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health Research Program
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Athira Pharma
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): May 20, 2022
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: May 20, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Dementia; Cognition; Memory Loss; ATH-1017
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: ATH-1017-AD-0202; U1111-1255-9714 (Other Identifier: WHO (UTN)); 18PTC-R-589358 (Other Grant/Funding Number: Alzheimer's Association); 1R01AG068268-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No