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

• ClinicalTrials.gov Identifier: NCT04491006
• Recruitment Status: Completed
• First Posted: July 29, 2020
• Results First Posted: June 12, 2023
• Last Update Posted: June 12, 2023
• Sponsor: Athira Pharma
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Athira Pharma

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease; Dementia of Alzheimer Type	Drug: ATH-1017; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, parallel-group study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Translational Study of ATH-1017 in Subjects With Mild to Moderate Alzheimer's Disease
• Actual Study Start Date: November 23, 2020
• Actual Primary Completion Date: May 20, 2022
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Event-related Potential (ERP) P300 Latency at Baseline [ Time Frame: At Baseline (Day 1) ]
   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.

Secondary Outcome Measures :

1. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Baseline [ Time Frame: At Baseline (Day 1) ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Syrentis Clinical Research

Santa Ana, California, United States, 92705

United States, Florida

Premiere Research Institute

West Palm Beach, Florida, United States, 33407

United States, Georgia

iResearch Atlanta

Decatur, Georgia, United States, 30030

United States, New York

Neurological Associates of Albany

Albany, New York, United States, 12208

United States, Oregon

Center for Cognitive Health

Portland, Oregon, United States, 97225

United States, Washington

Evergreen Health Research Program

Kirkland, Washington, United States, 98034

University of Washington

Seattle, Washington, United States, 98104

Australia, New South Wales

Central Coast Neurosciences Research

Central Coast, New South Wales, Australia, 2261

St Vincent's Centre for Applied Medical Research, Translational Research Centre

Darlinghurst, New South Wales, Australia, 2010

Hammondcare Greenwich Hospital

Greenwich, New South Wales, Australia, 2065

KaRa MINDS

Macquarie Park, New South Wales, Australia, 2113

Australia, Victoria

HammondCare

Malvern, Victoria, Australia, 3144

Australia, Western Australia

Australian Alzheimer's Research Organization

Nedlands, Western Australia, Australia, 6009

Sponsors and Collaborators

Athira Pharma

National Institute on Aging (NIA)

  Study Documents (Full-Text)

Documents provided by Athira Pharma:

Study Protocol  [PDF] May 25, 2021

Statistical Analysis Plan  [PDF] June 2, 2022

More Information

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.

• Responsible Party: Athira Pharma
• ClinicalTrials.gov Identifier: NCT04491006
• 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 )
• First Posted: July 29, 2020
• Results First Posted: June 12, 2023
• Last Update Posted: June 12, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Athira Pharma:

Alzheimer's Disease; Cognition; Dementia; ATH-1017; Memory Loss

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders