Study to evaluate the efficacy, safety and tolerability of ORY-2001 in aggression in Alzheimer’s Disease (AD) – REIMAGINE-AD

Phase 1

Active, not recruiting

• Conditions: Aggression in Alzheimer’s Disease (AD); MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-001436-54-ES
• Lead Sponsor: Oryzon Genomics S. A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-30
• Study Completion: 2020-08-17
• Last Update Posted: 16 October 2023

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Men and women between 50-85 years of age

2. Diagnosis of Probable AD according to NIA-AA criteria (McKhann GM et al, 2011)

3. Body mass index (BMI) of at least 18.5 kg/m2

4. Significant or persistent agitation or aggression that was disruptive to patient’s daily living or put the patient in harm´s way for at least 3 days in the last 7 days prior to screening Visit and represents a change from the patient’s usual behaviour

5. MMSE score at Screening Visit =20

6. Ambulatory, non-hospitalised patients

7. Knowledgeable and reliable close relative/caregiver who will accompany the patient to all clinic Visits during the study

8. Stable pharmacological treatment of AD as per Summary of Product Characteristics (SmPC) for at least two months prior to screening

9. 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 sterilization, 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])
*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.

10. Signed informed consent by patient (or legal representative, if applicable) and signed informed consent by 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 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Failure to perform screening or baseline examinations
2. Hospitalization or change of concomitant medication one 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. Positive results for human immunodeficiency virus (HIV), active hepatitis C (positive detection of HCV RNA by nucleic acid test) or hepatitis B (hepatitis B surface antigen [HbsAg]) serology at the screening Visit, or significant medical history, signs and symptoms for tuberculosis (TB) according to the investigator criteria
5. 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-glutamyl-transferase [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. Non-controlled hypertension treatment
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
6. Disability that may prevent the patients from completing all study requirements; for instance, blindness, deafness, severe language difficulty
7. Chronic drug intake of:
a. Acenocoumarol, warfarin or digitoxin
b. Antidepressants (other than selective serotonin reuptake inhibitors [SSRIs], selective serotonin–norepinephrine reuptake inhibitors [SSNRIs], or other noradrenergic and/or serotoninergic antidepressant - see table 2 and table 3 -) in stable dose for at least one month before Screening Visit)
c. Antipsychotics (other than oral atypical antipsychotics in stable dose for at least one month before Screening Visit – See Table 2)
d. Mood stabilizers (i.e. lithium or valproic acid)
e. Systemic anticholinergics (inhaled anticholinergic are allowed)
f. Nootropics; for instance, racetams, amphetamines, methylphenidate, levodopa, preparations containing Gingko biloba or St John's Wort
g. Centrally active anti-hypertensive drugs (such as clonidine, a-methyldopa, guanidine, guanfacine)
h. Corticosteroids or immunosuppressant (only inhaled or topical suspension are allowed).
i. MAO inhibitors
j. Intake of medications acting directly on central nervous system that investigator considers relevant to the study
Note:
i) 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.
ii) Regular intake and in stable dose of gabapentine, topiramate, pregabaline for at least one month before Screening Visit are allowed.
8. Suspected or known drug or alcohol abuse.
9. Enrolment in another investigational study or intake of investigational drug within the previous 3 months.
10. Suicide attempt within the last year o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified