Testing the Safety and Preliminary Efficacy of the New Drug ORY-2001 in Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This is a Phase IIa study assessing the safety, tolerability and preliminary efficacy of ORY-2001 in mild to moderate Alzheimer's Disease patients.

Detailed Description
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This phase IIa study is a double-blind, randomized, parallel-group and multicenter study with a placebo-controlled 24-week treatment period followed by a no placebo-controlled 24-week extension period. It is planned to randomise 25 patients. In the double-blind placebo-controlled treatment period, all patients will be randomized between two doses of ORY-2001 and placebo. In the double-blind no placebo-controlled extension period, patients in the placebo arm will be re-allocated in one of the two different dose levels of ORY-2001. Randomization will be stratified by cognitive impairment severity. An independent Data Monitoring Committee (DMC) will review un-blinded safety data throughout the study.

Official Title
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A Multicentre,Randomised, Double-blind, Placebo-controlled, 3-arm, 24-week Parallel-group Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ORY-2001 in Patients With Mild-moderate Alzheimer's Disease

Conditions
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Mild to Moderate Alzheimer's Disease

Intervention / Treatment
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* Drug: ORY-2001 Low dose
* Drug: ORY-2001 High dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Probable Alzheimer's Disease (AD) diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria MMSE score at Screening and Baseline Visits of at least 16 and not greater than 26 Evidence of the AD pathophysiological process indicated by decreased levels of amyloid antigen binding (AB) and increased levels of total Tau protein or phospho-Tau protein in cerebrospinal fluid (CSF) Outpatient consulting a general practitioner, or a psychiatrist/neurologist/geriatrician Knowledgeable and reliable close relative/caregiver who will accompany the patient to all clinic visits during the study Daily treatment with the same acetylcholinesterase inhibitor on a stable dose Fertile male and female must use highly effective contraception, from the Screening Visit until 90 days after last dose. Signed informed consent by patient (or legal representative, if applicable) and a close relative/caregiver prior to the initiation of any study specific procedure Exclusion Criteria: Failure to perform screening or baseline examinations Hospitalization or change of concomitant medication 1 month prior to Screening visit or during Screening Period Clinical, laboratory or neuroimaging findings consistent with: Other primary degenerative dementia; Other neurodegenerative condition; Cerebrovascular disease; Other central nervous system diseases; A current Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of major depression, schizophrenia or bipolar disorder Positive results for tuberculosis, human immunodeficiency virus (HIV), hepatitis C or hepatitis B (hepatitis B surface antigen [HbsAg]) serology at the Screening Visit Clinically significant, advanced or unstable disease that may interfere with evaluation. Disability that may prevent the patients from completing all study requirements. Chronic drug intake of forbidden concomitant medication. Treatment with anti-amyloid beta or anti-Tau protein monoclonal antibodies or other disease modifying strategies within three months or five half-lives, whichever is longer, prior to the Screening Visit Treatment with an active vaccine targeting amyloid beta or Tau protein Suspected or known drug or alcohol abuse Metallic implants or any other cause precluding the performance of brain MRI Enrolment in another investigational study or intake of investigational drug within the previous 3 months since the last dose Suicide attempt within the last year or significant risk of suicide (in the opinion of the investigator, defined as a yes to suicidal ideation questions 4 or 5, or answering yes to suicidal behavior on the Columbia-Suicide Severity Rating Scale within the past 12 months) Any condition that in the opinion of the investigator makes the patient unsuitable for inclusion in the study

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Active Comparator: ORY-2001 Low dose<br>0.6mg ORY-2001 capsule | Drug: ORY-2001 Low dose<br>* 0.6mg ORY-2001 capsule<br>|
| Active Comparator: ORY-2001 High dose<br>1.2mg ORY-2001 capsule | Drug: ORY-2001 High dose<br>* 1.2mg ORY-2001 capsule<br>|
| Placebo Comparator: Placebo<br>Placebo capsule | Drug: Placebo<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs. | Week 24 | 
| Treatment Emergent Adverse Events | Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs. | Week 48 | 
| Withdrawn patients due to TEAEs | Number and percentage of withdrawn patients due to TEAEs | Week 24 | 
| Withdrawn patients due to TEAEs | Number and percentage of withdrawn patients due to TEAEs | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohen-Mansfield Agitation Inventory (CMAI) | Change from baseline to week 48 compared to placebo | 48 weeks | 
| Clinician version of the Apathy Evaluation Scale (AES-C) | Change from baseline to week 48 compared to placebo | 48 weeks | 
| 14-item Alzheimer's Disease Assessment Scale-Cognitive | Change from baseline to week 48 compared to placebo | 48 weeks | 
| Computerized Cognitive Test battery | Change from baseline to week 48 compared to placebo | 48 weeks | 
| Mini-Mental State Examination (MMSE) | Change from baseline compared to placebo | 48 weeks | 
| Clinical Dementia Rating Scale Sum of Boxes | Change from baseline to week 48 compared to placebo | 48 weeks | 
| Cornell Scale for Depression in Dementia (CSDD) | Change from baseline to week 48 compared to placebo | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, ORY-2001