ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease

NCT04488419 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ATH-1017-AD-0201
• Study Type: interventional
• Target: 554
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate safety and efficacy of fosgonimeton (ATH-1017) in the treatment of mild to moderate Alzheimer's disease with a randomized treatment duration of 26-weeks.

Conditions

Alzheimer Disease; Dementia of Alzheimer Type

Keywords

Alzheimer's Disease; Cognition; Dementia; ATH-1017; LIFT AD; Fosgonimeton

Outcome Measures

Primary Outcomes (1)

• Global Statistical Test (GST) Score

  The Global Statistical Test (GST) score is a composite of cognition and function, calculated as the average of two change from baseline z-scores; the z-scores are calculated for the change from baseline scores for cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale \[ADAS-Cog11\]; lower value indicates improvement) and function (Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version \[ADCS-ADL23\] score; higher value indicates improvement). GST is a standardized score relative to the population mean. Therefore, a GST score of 0 is representative of the population mean. Since GST is a composite of two endpoints, a negative ADCS-ADL23 score is used in deriving GST. Therefore, a lower score indicates improvement, and a higher score indicates worsening. There are no defined clinically relevant thresholds for this GST score.

  Baseline and Week 26

Secondary Outcomes (3)

• Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline

  Baseline and Week 26

• Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline

  Baseline and Week 26

• Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline

  Baseline and Week 26

Study Arms (2)

Dosage

EXPERIMENTAL

Daily subcutaneous (SC) injection of 40mg ATH-1017

Drug: ATH-1017

Placebo

PLACEBO COMPARATOR

Daily subcutaneous (SC) injection of Placebo

Drug: Placebo

Interventions

ATH-1017 DRUG

Daily subcutaneous (SC) injection of ATH-1017 in a pre-filled syringe

Dosage

Placebo DRUG

Daily subcutaneous (SC) injection of Placebo in a pre-filled syringe

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m2 at Screening
• Reliable and capable support person/caregiver
• Treatment-free (subjects not receiving acetylcholinesterase inhibitor \[AChEI\] treatment), defined as:
• Treatment-naïve, OR
• Subjects who received an AChEI in the past and discontinued at least 4 weeks prior to Screening

You may not qualify if:

• History of significant neurologic disease, other than AD, that may affect cognition, or concurrent with the onset of dementia
• 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
• 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 cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable)
• Subject has either hypertension or symptomatic hypotension
• Clinically significant ECG abnormality at Screening
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) \<45 mL/min
• 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
• Acetylcholinesterase inhibitors in any dosage form

Sponsors & Collaborators

• Athira Pharma: lead

Study Sites (1)

University of Rochester-AD-CARE Program

Rochester, New York, 14620, United States

Location

Related Publications (2)

• 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.

  PMID: 21514250 BACKGROUND

• Reda SM, Setti SE, Berthiaume AA, Wu W, Taylor RW, Johnston JL, Stein LR, Moebius HJ, Church KJ. Fosgonimeton attenuates amyloid-beta toxicity in preclinical models of Alzheimer's disease. Neurotherapeutics. 2024 Jul;21(4):e00350. doi: 10.1016/j.neurot.2024.e00350. Epub 2024 Apr 9.

  PMID: 38599894 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Javier San Martin, CMO
• Organization: Athira Pharma

clinicaltrials@athira.com

1-866-725-0930

Study Officials

• Javier San Martin, MD

  Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parallel-group study

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 28, 2020
• Study Start: September 28, 2020
• Primary Completion: July 15, 2024
• Study Completion: July 15, 2024
• Last Updated: April 4, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)