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

Tracking Information

• First Submitted Date: July 23, 2020
• First Posted Date: July 29, 2020
• Results First Submitted Date: May 20, 2023
• Results First Posted Date: June 12, 2023
• Last Update Posted Date: June 12, 2023
• Actual Study Start Date: November 23, 2020
• Actual Primary Completion Date: May 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2023)

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.

Original Primary Outcome Measures (submitted: July 27, 2020)

Event-Related Potential [ Time Frame: Week 26 ]

Event-related potential (ERP) P300 latency

Current Secondary Outcome Measures (submitted: May 20, 2023)

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.

Original Secondary Outcome Measures (submitted: July 27, 2020)

Cognition [ Time Frame: 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of ATH-1017 in Mild to Moderate Alzheimer's Disease
• Official Title: A Randomized, Placebo-Controlled, Translational Study of ATH-1017 in Subjects With Mild to Moderate Alzheimer's Disease
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Condition

• Alzheimer Disease
• Dementia of Alzheimer Type

Intervention

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

Study Arms

• Experimental: Low Dose
  Daily subcutaneous (SC) injection of Low Dose ATH-1017
  Intervention: Drug: ATH-1017
• Experimental: High Dose
  Daily subcutaneous (SC) injection of High Dose ATH-1017
  Intervention: Drug: ATH-1017
• Placebo Comparator: Placebo
  Daily subcutaneous (SC) injection of Placebo
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 26, 2021): 77
• Original Estimated Enrollment (submitted: July 27, 2020): 75
• Actual Study Completion Date: May 20, 2022
• Actual Primary Completion Date: May 20, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Athira Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Athira Pharma
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Aging (NIA)
• Investigators: Not Provided
• PRS Account: Athira Pharma
• Verification Date: May 2023