Research Study for Participants with Mild Dementia as a Result of Alzheimer’s Disease

Do you have a loved one or friend who suffers from mild Dementia as a result of Alzheimer’s Disease?

This clinical research study is looking at the safety and effectiveness of an experimental treatment for people with early symptoms of dementia caused by Alzheimer’s Disease (AD).

Would you like them to take part in clinical research?

As a volunteer in a research study, your loved one will receive study-related medical care from the study doctor and regular follow-up of their condition to monitor the effectiveness of the care they will receive. The results of this research will be used to find out if the investigational medication being studied will be of benefit to other patients with Alzheimer’s disease, and whether it will be made widely available in Canada. Study volunteers are an important part of moving medical care forward.

Participants may qualify to participate in this study if they:

• Are between the ages of 60 and 85 years, inclusive
• Are an outpatient living at home or in an assisted living facility and are willing to attend all planned visits during the study.
• Have a study partner (who is not expected to change during the study) who will accompany the patient to the clinic, and/or be available by telephone at designated times, monitor administration of prescribed medications, control the minimum 2 hour daily light exposure requirement. The study partner must, in the opinion of the investigator, have enough contact with the participant to be able to perform the duties described above.
• Provide signed informed consent and have the capacity to provide informed consent as judged by the study investigator
• Have signed informed consent from the study partner.
• Meet NIA AA research criteria for probable AD (McKhann, Knopman et al. 2011).
• Have a clearly documented history of cognitive decline over at least 12 months.
• Have MRI/CT scan, performed within 12 months before Screening, with findings consistent with the diagnosis of AD without any other clinically significant comorbid pathologies. If MRI/CT was not performed within 12 months before Screening, it can be done during the screening period
• Are currently taking acetylcholinesterase inhibitors and or memantine for the treatment of AD, they may be enrolled if the patient has been taking such medication for at least 6 months before Visit 2 (Baseline) and is stable on any dose for the last 4 months prior to Baseline, and if the dose is not expected to change during study participation.
• Are not receiving acetylcholinesterase inhibitors, they may be enrolled but must be stable off acetylcholinesterase inhibitors for at least 3 months before Baseline, and agreeable to not starting throughout the first 26 weeks of the trial.
• Have a negative drug screen (benzodiazepines or opiates) at Screening. Positive drug screen of BZDs, is allowed only if the use is intermittent and drug intake was 4 days or more before the visit
• Female patients must have had last natural menstruation ≥ 24 months before Screening OR be surgically sterile.
• Male patients and their female spouse/partners who are of childbearing potential must agree to use highly effective methods of contraception, consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening, throughout the study and for 90 days post last dose, OR be surgically sterile.
• Are taking medications for non excluded concurrent medical conditions, they should be on a stable dose for at least 4 weeks before Screening. Patients taking allowed antidepressants should be on a stable dose for at least 3 months before Screening and throughout the study
• Have the ability and commitment to spend at least 2 hours per day exposed to daylight (preferably outside but can be next to a window if weather or personal situation does not permit).
• Participant and study partner have the ability to read and write in English or Spanish and have hearing, vision, and physical abilities adequate to perform assessments (corrective aids allowed).
• Participant and study partner are fully vaccinated for COVID 19 including booster doses as indicated (6 months post second dose). Having been diagnosed with COVID 19 after completing the initial full Covid vaccine would meet the requirements for a booster shot

Participants may not qualify to participate in this study if they:

• Have an alternative cause for dementia other than AD.
• Have evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD
• Have a concurrent psychiatric disorder that prevents his/her participation in the trial including but not limited to Schizophrenia, Bipolar and related disorders, Substance use disorders within the past 2 years, major depression, etc.
• Have a history of uncontrolled or untreated cardiovascular, endocrine, gastrointestinal, respiratory, or rheumatologic disorders within the past 5 years.
• Have a history of severe agitation and medically treated agitation.
• Have a history of serious infectious disease including:
  • Neurosyphilis
  • Meningitis
  • Encephalitis
• Have a history of a primary or recurrent malignant disease that has not been in remission for > 5 years prior to the Screening visit, with the exceptions of excised cutaneous squamous cell carcinoma in situ, basal cell carcinoma without recurrences; and history of intraductal breast cancer, cervical carcinoma in situ, or in situ prostate cancer resected over 5 years previously
• Have severe pain that is likely to interfere with sleep (in the opinion of the investigator).
• Have any concomitant documented progressive disease likely to interfere with the conduct of the study, particularly:
  • Liver disease with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gamma glutamyltransferase (GGT) > 3 times the upper limits of normal (ULN)
  • Total bilirubin > 3 times the ULN
  • Mean corpuscular volume > 95 µ3 if due to chronic alcoholism
  • Renal failure with creatinine < 30 ml / min
• Are using benzodiazepines or other sedative hypnotics during the 2 weeks before Screening
• Have a history of chronic use (more than 3 months of continuous use) and abuse of benzodiazepines or other sedative hypnotics.
• Use of any kind of melatonin/melatonin agonist during the 2 weeks before Screening
• Have known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists.
• Have clinically significant abnormal laboratory findings that have not been approved by the study safety officer.
• Have persistent bradycardia (heart beat < 50 bpm) or tachycardia (heart beat > 100 bpm).
• Have atrioventricular block (type II/Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or a marked prolongation of QTc interval (repeated demonstration in ECGs of QTc interval > 450 msec for males and > 470 msec for females using Fridericia’s formula: QTc = QT/cube root of RR).
• Have other serious diseases that could interfere with patient assessment, in the opinion of the investigator.
• Have untreated B12 and/or folic acid deficiency.
• Have participated in a clinical trial with any investigational agent within 3 months before Screening. Participants in any former monoclonal antibody clinical trial for AD are not eligible until 6 months after the last visit of the previous study. Patients who have received active vaccine for AD in the past will be excluded.
• Have a body mass index (BMI) above 35 or below 18.
• Lifestyle exclusions:
  • Patients unwilling to limit alcohol intake to less than 30 g of pure alcohol per day (see Appendix 1) and to abstain after 2000h throughout the study
  • Patients unwilling to be exposed to at least 2 hours of daylight each day
  • Divergence from the accepted level of study medication compliance (70% 130% of expected consumption) as verified at Visit 2
  • Patients consuming more than 7 cups of tea or coffee (or equivalent amount of caffeine [650 mg] in other caffeinated beverages) per day
  • Patients with an irregular lifestyle or life pattern (e.g., shift workers, patients likely to be jet lagged)
  • Patients with evidence of serious risk of suicide based on the Columbia-Suicide Severity Rating Scale, i.e., active suicidal ideation with some intent to act, with or without a specific plan (a positive response to Suicidal Ideation Items 4 or 5) in the 6 months prior to Screening, OR with evidence of suicidal behavior in the 2 years prior to Screening (a positive response to any of the 5 Suicidal Behavior Items {actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior}), OR who, in the opinion of the investigator, present a serious risk of suicide

There are other eligibility requirements that the study doctor will review. Only the study doctor can finally determine whether they are eligible to participate in the study or not.