ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies (SHAPE Trial)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and treatment effects of fosgonimeton (ATH-1017) in subjects with Parkinson's Disease Dementia or Dementia with Lewy Bodies, with a randomized treatment duration of 26 weeks.

Detailed Description
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The study is designed to evaluate the safety and treatment effects of ATH-1017 in subjects with Parkinson's Disease Dementia or Dementia with Lewy Bodies, with a randomized, double-blind, placebo-controlled, parallel-arm treatment duration of 26 weeks.

Official Title
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A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment in Subjects With Parkinson's Disease Dementia or Dementia With Lewy Bodies

Conditions
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Parkinson Disease Dementia, Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: ATH-1017
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with confirmed diagnosis of Parkinson's disease or Dementia with Lewy Bodies MoCA score 11 to 23, inclusive, at screening Probable Parkinson's Disease Dementia or Lewy Body Dementia BMI between ≥ 16and ≤ 35 kg/m2 for females and between≥ 18 and ≤ 35 kg/m2 for males at Screening Reliable and capable support person/caregiver, who is willing to accept responsibility for supervising the treatment or, if required, administering study drug, and assessing the condition of the subject throughout the study in accordance with all protocol requirements Exclusion Criteria: Hoehn-Yahr stage 5 History of significant neurological disease other than PDD or DLB that may affect cognition at onset of dementia Subjects on deep brain stimulation History of brain MRI scan indicative of any other significant abnormality History of unexplained loss of consciousness, and epileptic fits Hearing test result considered unacceptable for auditory ERP P300 assessment Diagnosis of severe major depressive disorder even without psychotic features (GDS score [15-item scale] >7 at Screening) Significant suicide risk based on C-SSRS Significant psychosis (according to Diagnostic and Statistical Manual of Mental Disorders) Moderate or severe substance abuse disorder (according to DSM-5) 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) Clinically significant ECG abnormality at Screening Chronic kidney disease (eGFR < 45 mL/min using Cockcroft-Gault formula) 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 at any dose or combination Donepezil at 23 mg

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40mg Dose<br>Daily subcutaneous injection of 40mg ATH-1017 | Drug: ATH-1017<br>* Daily subcutaneous injection of ATH-1017 in a pre-filled syringe<br>|
| Experimental: 70mg Dose<br>Daily subcutaneous injection of 70mg ATH-1017 | Drug: ATH-1017<br>* Daily subcutaneous injection of ATH-1017 in a pre-filled syringe<br>|
| Placebo Comparator: Placebo<br>Daily subcutaneous injection of Placebo | Drug: Placebo<br>* Daily subcutaneous injection of Placebo in a pre-filled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall treatment effect of ATH-1017 as reflected by the Global Statistical Test | As reflected by the composite Global Statistical Test (GST) | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-Related Potential | Event-related potential (ERP) P300 latency change from baseline | Week 2, 12, 26 | 
| Cognition | Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog13] change from baseline (Range of 0 to 85, where 0 is least impairment and 85 is most severe impairment) | Week 2, 12, 20, and 26 | 
| Clinical Global Impression of Change | Clinical Global Impression of Change (CGI-C) change from baseline (Range of 1 to 7, where 1 is marked improvement and 7 is marked worsening) | Week 12 and 26 | 
| Activities of Daily Living | Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version [ADCS-ADL23] change from baseline (Range of 0 to 78, where a higher score indicates greater function) | Week 12 and 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HGF/MET, Parkinson's Disease Dementia, Dementia with Lewy Bodies, Dementia, Hepatocyte Growth Factor, Neurotrophic, ATH-1017, Event-Related Potential, ERP P300