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

• ClinicalTrials.gov Identifier: NCT03867253
• Recruitment Status: Completed
• First Posted: March 7, 2019
• Last Update Posted: March 5, 2021
• Sponsor: Oryzon Genomics S.A.
• Collaborator: Alzheimer's Drug Discovery Foundation
• Information provided by (Responsible Party): Oryzon Genomics S.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mild to Moderate Alzheimer's Disease	Drug: ORY-2001 Low dose; Drug: ORY-2001 High dose; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 16, 2019
• Actual Primary Completion Date: November 12, 2020
• Actual Study Completion Date: November 12, 2020

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo; Placebo capsule	Drug: Placebo; Placebo capsule

Outcome Measures

Primary Outcome Measures :

1. Treatment Emergent Adverse Events [ Time Frame: Week 24 ]
   Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs.
2. Treatment Emergent Adverse Events [ Time Frame: Week 48 ]
   Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs.
3. Withdrawn patients due to TEAEs [ Time Frame: Week 24 ]
   Number and percentage of withdrawn patients due to TEAEs
4. Withdrawn patients due to TEAEs [ Time Frame: Week 48 ]
   Number and percentage of withdrawn patients due to TEAEs

Secondary Outcome Measures :

1. Cohen-Mansfield Agitation Inventory (CMAI) [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo
2. Clinician version of the Apathy Evaluation Scale (AES-C) [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo
3. 14-item Alzheimer's Disease Assessment Scale-Cognitive [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo
4. Computerized Cognitive Test battery [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo
5. Mini-Mental State Examination (MMSE) [ Time Frame: 48 weeks ]
   Change from baseline compared to placebo
6. Clinical Dementia Rating Scale Sum of Boxes [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo
7. Cornell Scale for Depression in Dementia (CSDD) [ Time Frame: 48 weeks ]
   Change from baseline to week 48 compared to placebo

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

Alzheimer's Research and Treatment Center

Wellington, Florida, United States, 33414

United States, Georgia

Columbus Memory Center

Columbus, Georgia, United States, 31909

United States, New Jersey

Princeton Medical Institute

Princeton, New Jersey, United States, 08540

United States, Pennsylvania

Abington Neurological Associates Ltd.

Willow Grove, Pennsylvania, United States, 191090

Sponsors and Collaborators

Oryzon Genomics S.A.

Alzheimer's Drug Discovery Foundation

Investigators

• Study Director: Michael Ropacki, MD; Oryzon Genomics S.A.

More Information

• Responsible Party: Oryzon Genomics S.A.
• ClinicalTrials.gov Identifier: NCT03867253
• Other Study ID Numbers: CL05-ORY-2001US
• First Posted: March 7, 2019
• Last Update Posted: March 5, 2021
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Oryzon Genomics S.A.:

Alzheimer's Disease, ORY-2001

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders