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

Primary Purpose

Alzheimer Disease, Dementia of Alzheimer Type

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATH-1017
Placebo
Sponsored by
Athira Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's Disease, Cognition, Dementia, ATH-1017, Memory Loss

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Syrentis Clinical Research
  • Premiere Research Institute
  • iResearch Atlanta
  • Neurological Associates of Albany
  • Center for Cognitive Health
  • Evergreen Health Research Program
  • University of Washington
  • Central Coast Neurosciences Research
  • St Vincent's Centre for Applied Medical Research, Translational Research Centre
  • Hammondcare Greenwich Hospital
  • KaRa MINDS
  • HammondCare
  • Australian Alzheimer's Research Organization

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Low Dose

High Dose

Placebo

Arm Description

Daily subcutaneous (SC) injection of Low Dose ATH-1017

Daily subcutaneous (SC) injection of High Dose ATH-1017

Daily subcutaneous (SC) injection of Placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
July 23, 2020
Last Updated
May 20, 2023
Sponsor
Athira Pharma
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT04491006
Brief Title
A Study of ATH-1017 in Mild to Moderate Alzheimer's Disease
Acronym
ACT-AD
Official Title
A Randomized, Placebo-Controlled, Translational Study of ATH-1017 in Subjects With Mild to Moderate Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 23, 2020 (Actual)
Primary Completion Date
May 20, 2022 (Actual)
Study Completion Date
May 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Athira Pharma
Collaborators
National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Dementia of Alzheimer Type
Keywords
Alzheimer's Disease, Cognition, Dementia, ATH-1017, Memory Loss

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled, parallel-group study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Dose
Arm Type
Experimental
Arm Description
Daily subcutaneous (SC) injection of Low Dose ATH-1017
Arm Title
High Dose
Arm Type
Experimental
Arm Description
Daily subcutaneous (SC) injection of High Dose ATH-1017
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Daily subcutaneous (SC) injection of Placebo
Intervention Type
Drug
Intervention Name(s)
ATH-1017
Intervention Description
Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe
Primary Outcome Measure Information:
Title
Event-related Potential (ERP) P300 Latency at Baseline
Description
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.
Time Frame
At Baseline (Day 1)
Secondary Outcome Measure Information:
Title
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Baseline
Description
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.
Time Frame
At Baseline (Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Syrentis Clinical Research
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Premiere Research Institute
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33407
Country
United States
Facility Name
iResearch Atlanta
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Neurological Associates of Albany
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Center for Cognitive Health
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Evergreen Health Research Program
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Central Coast Neurosciences Research
City
Central Coast
State/Province
New South Wales
ZIP/Postal Code
2261
Country
Australia
Facility Name
St Vincent's Centre for Applied Medical Research, Translational Research Centre
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Hammondcare Greenwich Hospital
City
Greenwich
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
KaRa MINDS
City
Macquarie Park
State/Province
New South Wales
ZIP/Postal Code
2113
Country
Australia
Facility Name
HammondCare
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
Australian Alzheimer's Research Organization
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
21514250
Citation
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.
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A Study of ATH-1017 in Mild to Moderate Alzheimer's Disease

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