Clinical trial NCT04488419: ATH-1017 for Treatment of Mild to Moderate Alzheimer's Disease
Official title: A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment in Subjects With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer Disease
Dementia of Alzheimer Type
Keywords: Alzheimer's Disease
Cognition
Dementia
ATH-1017
LIFT AD
Fosgonimeton
Lead sponsor: Athira Pharma
Sponsor class: INDUSTRY
First posted: 2020-07-28
Enrollment: 554
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel-group study
Primary purpose: TREATMENT

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.

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)
* 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

Primary outcomes:
measure: Global Statistical Test (GST) Score
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline
timeFrame: Baseline and Week 26
measure: Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline
timeFrame: Baseline and Week 26
measure: Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline
timeFrame: Baseline and Week 26
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester-AD-CARE Program
state: New York
Study officials:
affiliation: Chief Medical Officer
name: Javier San Martin, MD
role: STUDY_DIRECTOR
References:
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.