Mild to Moderate Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, ORY-2001
Brief summary
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
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.
Interventions
DRUGORY-2001 Low dose
0.6mg ORY-2001 capsule
DRUGORY-2001 High dose
1.2mg ORY-2001 capsule
DRUGPlacebo
Placebo capsule
Sponsors
Alzheimer's Drug Discovery Foundation
Oryzon Genomics S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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: 1. Other primary degenerative dementia; 2. Other neurodegenerative condition; 3. Cerebrovascular disease; 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events | Week 24 | Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs. |
| Withdrawn patients due to TEAEs | Week 24 | Number and percentage of withdrawn patients due to TEAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 14-item Alzheimer's Disease Assessment Scale-Cognitive | 48 weeks | Change from baseline to week 48 compared to placebo |
| Computerized Cognitive Test battery | 48 weeks | Change from baseline to week 48 compared to placebo |
| Cohen-Mansfield Agitation Inventory (CMAI) | 48 weeks | Change from baseline to week 48 compared to placebo |
| Clinical Dementia Rating Scale Sum of Boxes | 48 weeks | Change from baseline to week 48 compared to placebo |
| Cornell Scale for Depression in Dementia (CSDD) | 48 weeks | Change from baseline to week 48 compared to placebo |
| Mini-Mental State Examination (MMSE) | 48 weeks | Change from baseline compared to placebo |
| Clinician version of the Apathy Evaluation Scale (AES-C) | 48 weeks | Change from baseline to week 48 compared to placebo |
Countries
United States
Outcome results
None listed