Alzheimer Disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
Oryzon Genomics S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women 50-85 years of age 2. Body mass index (BMI) of at least 18.5 kg/m2 3. Probable 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 4. MMSE score at Screening and Baseline Visits of at least 16 and not greater than 26 5. Evidence of the AD pathophysiological process indicated by decreased levels of amyloid AB and increased levels of total Tau protein or phospho-Tau protein in CSF 6. Ambulatory or ambulatory aided patient (i.e. walker or cane) 7. Outpatient consulting a general practitioner, or a phsychiatrist/neurologist/geriatrician 8. Formal education for more than 6 years 9. Knowledgeable and reliable close relative/caregiver who will accompany the patient to all clinic visits during the study 10. Daily treatment with the same acetylcholinesterase inhibitor (oral donepezil, oral or transdermal patch rivastigmine, or oral galantamine) for at least 6 months prior the Screening Visit and on a stable dose (i.e. the patient’s individual maintenance dose) for at least 4 months prior to the Screening Visit and throughout the Screening Period 11. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening – including anti-inflammatories 12. Fertile male and female must use highly efficient contraception, from the Screening Visit until 30 days after last dose of the IMP, defined as: a. A method with less than 1% failure rate (e.g. permanent sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner) OR b. The use of two methods of contraception (e.g. one barrier method [condom, diaphragm or cervical/vault caps] with spermicide and one hormonal contraceptive [e.g. combined oral contraceptives, patch, vaginal ring, injectable and implants]) 13. Signed informed consent by patient (or legal representative, if applicable) and a close relative/caregiver prior to the initiation of any study specific procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Failure to perform screening or baseline examinations 2. Hospitalisation or change of concomitant medication 1 month prior to Screening visit or during Screening Period 3. Member or immediate family of the study personnel or subordinate (or immediate family of a subordinate) to any of the study personnel 4. Patient under forced treatment 5. Clinical, laboratory or neuroimaging findings consistent with: a. Other primary degenerative dementia; for instance, dementia with Lewy bodies, frontotemporal dementia, Huntington’s disease, Jakob-Creutzfeld Disease, Down’s syndrome b. Other neurodegenerative condition; for instance, Parkinson’s disease, amyotrophic lateral sclerosis c. Cerebrovascular disease: major infarct, one strategic or more than 2 lacunar infarcts or extensive white matter lesions as described by local radiologist d. Other central nervous system diseases; for instance, severe head trauma, tumours, subdural hematoma or other space occupying processes 6. A current DSM-V diagnosis of major depression, schizophrenia or bipolar disorder 7. Positive results for tuberculosis, human immunodeficiency virus (HIV), hepatitis C or hepatitis B (hepatitis B surface antigen [HbsAg]) serology at the Screening Visit 8. Clinically significant, advanced or unstable disease that may interfere with evaluation: a. Seizures disorders b. Respiratory insufficiency (partial pressure of oxygen 50 mmHg) c. Hepatic impairment (serum total bilirubin value, serum alanine aminotransferase [ALT], serum aspartate aminotransferase [AST] and gamma-glutamyltransferase [GGT] 1.5 x upper limit of normal [ULN]) d. Renal insufficiency (serum creatinine >2mg/dl) e. Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 6 months before Screening Visit) f. Hypertension treatment with more than 2 drugs g. Atrioventricular block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males >450 msec and females >470 msec) h. Uncontrolled diabetes (Hb1Ac >7.5) i. Haematological disorders, especially thrombocytopenia (platelets <75 000/mm3) and neutropenia (neutrophils <1 500/mm3) j. Malignant tumours within the last 5 years 9. Disability that may prevent the patients from completing all study requirements; for instance, blindness, deafness, severe language difficulty 10. Chronic drug intake of: a. Acenocoumarol, warfarin or digitoxin b. Antidepressants (other than selective serotonin reuptake inhibitors [SSRIs] or selective serotonin–norepinephrine reuptake inhibitors [SSNRIs]), neuroleptics or major sedatives. Note: Patients may be included if treated with a stable dose of SSRIs or SSNRIs antidepressants for at least six months before Screening Visit. As specified in the AChEI treatment Summary of Product Characteristics; precautions should be taken when administering fluoxetine c. Memantine d. Systemic anticholinergics e. Nootropics; for instance, racetams, anphetamines, metylphenidate, levodopa, atomoxetina, preparations containing Gingko biloba or St John's Wort f. Centrally active anti-hypertensive drugs (such as clonidine, a-methyldopa, guanidine, guanfacine) g. Corticosteroids or immunosuppressant h. Antipsychotics i. MAO inhibitors j. No regular intake of medications acting directly on central nervous system that investigator consider relevant to the study 11. Treatment with anti-amyloid beta or anti-Tau protein mono
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of two doses of ORY-2001 in patients with mild-moderate Alzheimer's Disease;Secondary Objective: To investigate the effect of two doses of ORY-2001 on the clinical domains of Alzheimer´s Disease;Primary end point(s): Safety • Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) up to Week 24 and Week 48 • Number, frequency and severity of Serious TEAEs up to Week 24 and Week 48 • Number and percentage of withdrawn patients due to TEAEs up to Week 24 and Week 48 • Change from baseline to Week 24 and Week 48 in physical examination, vital signs and ECG parameters • Frequency of physical examination parameters, vital signs and ECG parameters of potential clinical concern throughout the study period • Change from baseline to Week 24 and Week 48 in clinical laboratory parameters (haematology, including platelets) and clinical chemistry • Frequency of clinical laboratory parameters (haematology, including platelets, and clinical chemistry) of potential clinical concern throughout the study period • Use of concomitant medication throughout the study period;Timepoint(s) of evaluation of this end point: 24 and 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • Change from Baseline to Week 24 and Week 48 compared to placebo in the Cohen-Mansfield Agitation Inventory (CMAI) • Change over time compared to placebo in the CMAI • Change from Baseline to Week 24 and Week 48 compared to placebo in the Clinician version of the Apathy Evaluation Scale (AES-C) • Change over time compared to placebo in the AES-C • Change from Baseline to Week 12, Week 24 and Week 48 compared to placebo in the 14-item Alzheimer's Disease Assessment Scale-Cognitive • Change from Baseline to Week 12, Week 24 and Week 48 compared to placebo in the Computerised Cognitive Test battery • Change from Baseline to Week 24 and Week 48 compared to placebo in the MMSE • Change from Baseline to Week 24 and Week 48 compared to placebo in the Clinical Dementia Rating Scale Sum of Boxes • Change from Baseline to Week 24 and Week 48 compared to placebo in the Cornell Scale for Depression in Dementia (CSDD) • Change over time in compared to placebo the CSDD;Timepoint(s) of evaluation of this end point: 12, 24, 48 weeks | — |
Countries
France, Spain, United Kingdom
Contacts
Public ContactClinical Operations
Oryzon Genomics S.A.
Outcome results
None listed