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

Alzheimer Disease Clinical Trial

— ACT-AD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04491006
• Other study ID #: ATH-1017-AD-0202
• Secondary ID: U1111-1255-97141
• Status: Completed
• Phase: Phase 2
• Start date: November 23, 2020
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2023
• Source: Athira Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: May 20, 2022
• Est. primary completion date: May 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia
• Dementia of Alzheimer Type

Intervention

Drug:
• ATH-1017
Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe
• Placebo
Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe

Locations

Country	Name	City	State
Australia	Central Coast Neurosciences Research	Central Coast	New South Wales
Australia	St Vincent's Centre for Applied Medical Research, Translational Research Centre	Darlinghurst	New South Wales
Australia	Hammondcare Greenwich Hospital	Greenwich	New South Wales
Australia	KaRa MINDS	Macquarie Park	New South Wales
Australia	HammondCare	Malvern	Victoria
Australia	Australian Alzheimer's Research Organization	Nedlands	Western Australia
United States	Neurological Associates of Albany	Albany	New York
United States	iResearch Atlanta	Decatur	Georgia
United States	Evergreen Health Research Program	Kirkland	Washington
United States	Center for Cognitive Health	Portland	Oregon
United States	Syrentis Clinical Research	Santa Ana	California
United States	University of Washington	Seattle	Washington
United States	Premiere Research Institute	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Athira Pharma	National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)