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

• Sponsor: Athira Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04491006
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 77
• Locations: 13
• Arms: 3
• Actual Duration (Months): 17.8
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is designed to evaluate treatment effects of fosgonimeton (ATH-1017) 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
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double-blind, placebo-controlled, parallel-group studyRandomized, 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: Nov 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 [Week 26]

   Event-related potential (ERP) P300 latency

Secondary Outcome Measures

1. Cognition [Weeks 2, 6, 12, 20, and 26]

   Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog11] (Range of 0 to 70, where 0 is least impairment and 70 is most severe impairment)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Syrentis Clinical Research	Santa Ana	California	United States	92705
2	Premiere Research Institute	West Palm Beach	Florida	United States	33407
3	iResearch Atlanta	Decatur	Georgia	United States	30030
4	Neurological Associates of Albany	Albany	New York	United States	12208
5	Center for Cognitive Health	Portland	Oregon	United States	97225
6	Evergreen Health Research Program	Kirkland	Washington	United States	98034
7	University of Washington	Seattle	Washington	United States	98104
8	Central Coast Neurosciences Research	Central Coast	New South Wales	Australia	2261
9	St Vincent's Centre for Applied Medical Research, Translational Research Centre	Darlinghurst	New South Wales	Australia	2010
10	Hammondcare Greenwich Hospital	Greenwich	New South Wales	Australia	2065
11	KaRa MINDS	Macquarie Park	New South Wales	Australia	2113
12	HammondCare	Malvern	Victoria	Australia	3144
13	Australian Alzheimer's Research Organization	Nedlands	Western Australia	Australia	6009

Sponsors and Collaborators

• Athira Pharma
• National Institute on Aging (NIA)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

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; 18PTC-R-589358; 1R01AG068268-01
• First Posted: Jul 29, 2020
• Last Update Posted: Jul 7, 2022
• Last Verified: Jul 1, 2022

• 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

Study Results

No Results Posted as of Jul 7, 2022