A study to evaluate the safety, tolerability and preliminary efficacy of ORY-2001 in patients with mild-moderate Alzheimer's Disease
- Conditions
- Alzheimer DiseaseMedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2017-004893-32-GB
- Lead Sponsor
- Oryzon Genomics S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 125
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.Prior treatment:
a. 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 (applicable for centres located in Spain, France and UK) or
b.Patients with no previous AD treatment (i.e.: AChEI or memantine) before the Screening Visit. These AD treatment-naïve patients should not receive AD treatment other than ORY-2001 at any moment from Screening Visit and throughout the study (only applicable for centres located in France and UK)
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 effective contraception, from the Screening Visit until 90 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, 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])
*Following menarche and until becoming post-menopausal unless permanently sterile. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause
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 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 63
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-5 diagnosis of major depression, schizophrenia or bipolar disorder
7. Positive results for tuberculosis (the status must be determined as usual clinical practice, i.e. by medical history, signs and symptoms), 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 <60 mm Hg and partial
pressure of carbon dioxide >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 other than basal cell or Stage 1 squamous cell carcinoma of the skin
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 sedatives. Note 2: Short and medium half-life oral benzodiazepines (alprazolam, lorazepam, midazolam, oxazepam,
temazepam) and Z-drugs (zaleplon, zolpidem, zoplicone) are allowed in occasional short term prescription. Patients should not take these medications within 24 hours before any study visit.)
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method