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

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

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.

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