Clinical trial NCT04491006: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Dementia of Alzheimer Type
Keywords: Alzheimer's Disease
Cognition
Dementia
ATH-1017
Memory Loss
Lead sponsor: Athira Pharma
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
First posted: 2020-07-29
Enrollment: 77
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 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.

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

Primary outcomes:
measure: Event-related Potential (ERP) P300 Latency at Baseline
timeFrame: At Baseline (Day 1)
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Baseline
timeFrame: At Baseline (Day 1)
Other outcomes:
Locations:
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Albany
country: United States
facility: Neurological Associates of Albany
state: New York
city: Portland
country: United States
facility: Center for Cognitive Health
state: Oregon
city: Kirkland
country: United States
facility: Evergreen Health Research Program
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Central Coast
country: Australia
facility: Central Coast Neurosciences Research
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Centre for Applied Medical Research, Translational Research Centre
state: New South Wales
city: Greenwich
country: Australia
facility: Hammondcare Greenwich Hospital
state: New South Wales
city: Macquarie Park
country: Australia
facility: KaRa MINDS
state: New South Wales
city: Malvern
country: Australia
facility: HammondCare
state: Victoria
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Organization
state: Western Australia
Study officials:
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.