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

Mild to Moderate Alzheimer's Disease Clinical Trial

— ETHERAL-US  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03867253
• Other study ID #: CL05-ORY-2001US
• Status: Completed
• Phase: Phase 2
• Start date: May 16, 2019
• Est. completion date: November 12, 2020

Study information

• Verified date: July 2020
• Source: Oryzon Genomics S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 12, 2020
• Est. primary completion date: November 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Mild to Moderate Alzheimer's Disease

Intervention

Drug:
• ORY-2001 Low dose
0.6mg ORY-2001 capsule
• ORY-2001 High dose
1.2mg ORY-2001 capsule
• Placebo
Placebo capsule

Locations

Country	Name	City	State
United States	Columbus Memory Center	Columbus	Georgia
United States	Princeton Medical Institute	Princeton	New Jersey
United States	Alzheimer's Research and Treatment Center	Wellington	Florida
United States	Abington Neurological Associates Ltd.	Willow Grove	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Oryzon Genomics S.A.	Alzheimer's Drug Discovery Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Emergent Adverse Events	Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs.	Week 24
Primary	Treatment Emergent Adverse Events	Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs.	Week 48
Primary	Withdrawn patients due to TEAEs	Number and percentage of withdrawn patients due to TEAEs	Week 24
Primary	Withdrawn patients due to TEAEs	Number and percentage of withdrawn patients due to TEAEs	Week 48
Secondary	Cohen-Mansfield Agitation Inventory (CMAI)	Change from baseline to week 48 compared to placebo	48 weeks
Secondary	Clinician version of the Apathy Evaluation Scale (AES-C)	Change from baseline to week 48 compared to placebo	48 weeks
Secondary	14-item Alzheimer's Disease Assessment Scale-Cognitive	Change from baseline to week 48 compared to placebo	48 weeks
Secondary	Computerized Cognitive Test battery	Change from baseline to week 48 compared to placebo	48 weeks
Secondary	Mini-Mental State Examination (MMSE)	Change from baseline compared to placebo	48 weeks
Secondary	Clinical Dementia Rating Scale Sum of Boxes	Change from baseline to week 48 compared to placebo	48 weeks
Secondary	Cornell Scale for Depression in Dementia (CSDD)	Change from baseline to week 48 compared to placebo	48 weeks