ETHERAL-US

CompletedPhase 2

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

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

Lead sponsor

Oryzon Genomics S.A.

Asset

ORY-2001

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE ≥16•Study partner/caregiver required•AD symptomatic therapy: stable

Primary endpoints

•Treatment Emergent Adverse Events•Withdrawn patients due to TEAEs

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDCL05-ORY-2001US

NCT IDNCT03867253

Timeline

Milestones

Study first posted2019-03-07actual

Study start2019-05-16actual

Primary completion2020-11-12actual

Study completion2020-11-12actual

Last update posted2021-03-05actual

Assets

Drug assets

ORY-2001

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (11)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Behavior / neuropsychiatric

Global cognition

Safety / tolerability / PK

Global cognition

2 endpoints

Secondary/protocol endpoint

Mini-Mental State Examination (MMSE)

Time frame:48 weeks

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Clinical Dementia Rating Scale Sum of Boxes

Time frame:48 weeks

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Behavior / neuropsychiatric

3 endpoints

Secondary/protocol endpoint

Cohen-Mansfield Agitation Inventory (CMAI)

Time frame:48 weeks

change from baseline, improvement

Secondary/protocol endpoint

Clinician version of the Apathy Evaluation Scale (AES-C)

Time frame:48 weeks

change from baseline, improvement

Secondary/protocol endpoint

Cornell Scale for Depression in Dementia (CSDD)

Time frame:48 weeks

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Primary/protocol endpoint

Treatment Emergent Adverse Events

Time frame:Week 24

event count, event

Primary/protocol endpoint

Treatment Emergent Adverse Events

Time frame:Week 48

event count, event

Other (unclassified)

4 endpoints

Primary/protocol endpoint/low confidence

Withdrawn patients due to TEAEs

Time frame:Week 24

threshold achievement, improvement

Primary/protocol endpoint/low confidence

Withdrawn patients due to TEAEs

Time frame:Week 48

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

14-item Alzheimer's Disease Assessment Scale-Cognitive

Time frame:48 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Computerized Cognitive Test battery

Time frame:48 weeks

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.