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

Phase 2

Completed

Conditions: Alzheimer Disease
Dementia of Alzheimer Type

Interventions: Drug: ATH-1017
Drug: Placebo

Registration Number: NCT04488419

Lead Sponsor: Athira Pharma

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.

Detailed Description: The study is designed to evaluate safety and efficacy of ATH-1017 in mild to moderate AD subjects, with randomized, parallel-arm treatment duration of 26 weeks, and based on clinical diagnostic criteria of Alzheimer's disease. Clinical efficacy is demonstrated by improvement in cognition and global/functional assessments comparing treatment to placebo.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 554

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)
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

Key

Exclusion Criteria

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
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dosage	ATH-1017	Daily subcutaneous (SC) injection of 40mg ATH-1017
Placebo	Placebo	Daily subcutaneous (SC) injection of Placebo

Primary Outcome Measures

Name	Time	Method
Global Statistical Test (GST) Score	Baseline and Week 26	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.

Secondary Outcome Measures

Name	Time	Method
Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline	Baseline and Week 26	The ADCS-ADL23 is a 23-item assessment of functional impairment in terms of activities of daily living administered to the support person/caregiver. It comprises 23 questions about the subject's involvement and level of performance across items representing daily living. The questions range from basic to instrumental activities of daily living. Each item is rated from the highest level of independent performance to complete loss. The total score range is from 0 to 78, with lower scores indicating greater functional impairment. Baseline was defined as Day 1.
Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline	Baseline and Week 26	Neurofilament light chain (NfL) is an objective biomarker of neurodegeneration and was measured to quantitatively support the evaluation of ATH-1017. Higher concentrations of NfL in plasma are associated with neurodegeneration.
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline	Baseline and Week 26	The ADAS-Cog11 was designed to measure cognitive symptom change in participants with Alzheimer's Disease (AD) and consisted of 11 tasks. 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.