Aggression in Alzheimer’s Disease (AD) MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Vafidemstat
Product Code: ORY-2001
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ORY-2001 (Vafidemstat)
CAS Number: 1357247-95-0
Other descriptive name: ORY-2001 (Vafidemstat)
Sponsors
Oryzon Genomics S. A.
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of ORY-2001 in aggression in an AD population;Secondary Objective: - To investigate other changes on behaviour, cognition and caregiver burden - To evaluate the safety and tolerability of ORY-2001 in an AD population;Primary end point(s): 1. Change from baseline to week 8 in NPI-4 A/A(i.e. the 4 item Neuropsychiatric Inventory Questionnaire Agitation/Aggression Subscale: agitation/aggression, disinhibition, irritability/lability, aberrant motor disturbance) 2. Change over time in the NPI-4 A/A 3. Change from baseline to week 8 in the Cohen-Mansfield Agitation inventory (CMAI) 4. Change over time in the CMAI 5. Change from baseline to week 8 in the Clinical Global Impression-Agitation/Aggression (CGI-A/A) 6. Change over time in the CGI-A/A;Timepoint(s) of evaluation of this end point: 13 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline to week 8 in NPI 2. Change from baseline to week 8 in Zarit Burden Interview (ZBI) 3. Change from baseline to week 8 in MMSE 4. Number, frequency and severity of Adverse Drug Reactions (ADRs) up to week 8 5. Number, frequency and severity of Serious ADRs up to Week 8 6. Number and percentage of withdrawn participants due to ADRs up to Week 8 7. Change from baseline to Week 8 in physical examination, vital signs and ECG parameters 8. Frequency of physical examination parameters, vital signs and ECG parameters of potential clinical concern throughout the study Period 9. Change from baseline to Week 8 in clinical laboratory parameters (hematology, including platelets) and clinical chemistry 10. Frequency of clinical laboratory parameters (hematology and clinical chemistry) of potential clinical concern throughout the study Period 11. Use of concomitant medication throughout the study Period;Timepoint(s) of evaluation of this end point: 13 weeks | — |
Countries
Spain
Contacts
Public ContactRoger Bullock
Oryzon Genomics S. A.
Outcome results
None listed