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

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

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

Study Overview

• Status: Completed
• Conditions: Mild to Moderate Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: ORY-2001 Low dose; Drug: ORY-2001 High dose

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States, 191090
      • Abington Neurological Associates LTD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo capsule	Drug: Placebo; Placebo capsule
ACTIVE_COMPARATOR: ORY-2001 Low dose; 0.6mg ORY-2001 capsule	Drug: ORY-2001 Low dose; 0.6mg ORY-2001 capsule
ACTIVE_COMPARATOR: ORY-2001 High dose; 1.2mg ORY-2001 capsule	Drug: ORY-2001 High dose; 1.2mg ORY-2001 capsule

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oryzon Genomics S.A.
• Collaborators: Alzheimer's Drug Discovery Foundation
• Investigators: Study Director: Michael Ropacki, MD, Oryzon Genomics S.A.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 16, 2019
• Primary Completion (ACTUAL): November 12, 2020
• Study Completion (ACTUAL): November 12, 2020

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (ACTUAL): March 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 5, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Alzheimer's Disease, ORY-2001
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CL05-ORY-2001US

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No