Clinical trial: Efficacy and Safety of AD-35 in Treatment of Subjects With Mild to Moderate Alzheimer's Disease (NCT03625401)

Eligibility criteria:
Inclusion Criteria:

          1. Subjects must be diagnosed with probable AD in accordance with the National Institute
             on Aging and Alzheimer's Association (NIA-AA) (2011) criteria.

          2. Subjects must have a Mini-Mental State Examination (MMSE) score of ≥15 and ≤26 at
             screening and baseline.

          3. Subjects must have a brain magnetic resonance imaging (MRI) scan that is consistent
             with a clinical diagnosis of probable AD.

          4. Subjects should not have received Aβ-based or tau-based treatment for AD.

          5. Subjects who were previously treated with Acetyl cholinesterase inhibitor (AChEI) or
             memantine, must have been off of the therapy for at least 3 months prior to baseline
             assessments. Subjects who have been taking AChEI or memantine for ≤7 days may be
             considered for enrollment in this study.

          6. For subjects who are currently receiving other non-excluded prescription or
             over-the-counter medications that might affect cognitive function (eg,
             non-anticholinergic antidepressants, atypical antipsychotics, non-benzodiazepine
             anxiolytics, soporifics, centrally acting anticholinergic antihistamines, centrally
             acting anticholinergic antispasmodics):

               -  Treatment must be at a stable dose for ≥1 month prior to randomization and
                  throughout the duration of the study.

               -  Treatment given intermittently and on a short-term basis must not be administered
                  within 5 half-lives prior to the screening of neurocognitive assessments.

          7. Subjects must be male or female between 50 years to 85 years of age (inclusive), at
             screening.

          8. Female subjects must be post-menopausal for at least 2 consecutive years or surgically
             sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at
             least 6 months prior to screening.

          9. Male subjects with partners of reproductive potential must agree to use a reliable
             means of contraception (eg, minimum condom + spermicide) during the study and 30 days
             after discontinuing the study drug.

         10. Subjects must have a reliable caregiver with contact at least 3 times per week
             (combination of face to face visits and telephone contact acceptable). The caregiver
             must be able to oversee the subject's compliance with study drug and participate in
             the subject's clinical assessment, to provide meaningful input into the NPI, ADCS-ADL,
             and CIBIC+.

         11. Subjects (or subject's legally authorized representatives and their caregivers) must
             be able to provide informed consent.

         12. Subjects (and their caregivers) must be able to read, write, speak, and understand
             English to ensure compliance with cognitive testing and study visit procedures.

         13. Subjects (and their caregivers) must be willing and able to comply with the protocol's
             requirements.

         14. Subjects must weigh between 45 kg and 90 kg (inclusive), at screening.

         15. Subjects must be in general good health in the opinion of the Investigator, based on
             medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) in
             triplicate, and clinical laboratory values.

        Exclusion Criteria:

          1. Lack of peripheral venous access.

          2. Uncorrected impairment of vision or hearing that would preclude the subject from
             taking tests, or subjects lacking the ability to communicate.

          3. Inability to tolerate MRI procedures or contraindication to MRI, including but not
             limited to MRI incompatible pacemakers; implantable cardioverter defibrillators;
             cochlear implants; cerebral aneurysm clips; implanted infusion pumps; implanted nerve
             stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical
             implants; or any other clinical history or examination finding that, in the judgment
             of the Investigator, would pose a potential hazard in combination with MRI.

          4. Severe or unstable medical condition that, in the opinion of the Investigator or
             Sponsor, would interfere with the subject's ability to complete the study assessments.

          5. History or presence of clinically evident vascular disease potentially affecting the
             brain (eg, stroke, clinically significant carotid or vertebral stenosis or plaque,
             aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous
             malformation).

          6. History of severe, clinically significant (persistent neurologic deficit or structural
             brain damage) central nervous system trauma (eg, cerebral contusion).

          7. History or presence of intracranial tumor (eg, meningioma, glioma).

          8. Presence of infections that affect the brain function or history of infections that
             resulted in neurologic sequelae (eg, syphilis, neuroborreliosis, viral or bacterial
             meningitis/encephalitis,human immunodeficiency virus encephalopathy).

          9. History or presence of systemic autoimmune disorders potentially causing progressive
             neurologic disease (eg, multiple sclerosis, lupus erythematosus, anti-phospholipid
             antibody syndrome, Behçet disease).

         10. History or presence of psychiatric disease other than AD that may affect cognition or
             prevent completion of study procedures, including but not limited to clinically
             significant major psychiatric disorder according to the criteria of the Diagnostic and
             Statistical Manual of Mental Disorders-V (DSM-V) (eg, major depression, schizophrenia,
             bipolar disorder).

             • A history of major depression is acceptable if no episode has been reported within
             the previous 5 years.

         11. History or presence of a neurologic disease other than AD that may affect cognition,
             including but not limited to Parkinson's disease, corticobasal degeneration, dementia
             with Lewy bodies, Creutzfeldt-Jakob disease, progressive supranuclear palsy,
             frontotemporal degeneration, Huntington's disease, normal pressure hydrocephalus, and
             hypoxia.

         12. History of seizures with the exception of childhood febrile seizures.

         13. Known or suspected history of alcohol or drug abuse within the previous 5 years (DSM-V
             criteria).

         14. Evidence of malignancies, acute infections, renal failure that requires dialysis, or
             other unstable medical disease not related to AD that in the Investigator's opinion
             would preclude subject participation.

             • This does not include any cancer (except adequately treated basal or squamous cell
             skin cancer) that is not being actively treated with anti-cancer drugs or radiotherapy
             as well as cancers that are considered to have low probability of recurrence (with
             supporting documentation of this from the treating oncologist, if possible).

         15. History or presence of atrial fibrillation that poses a risk for future stroke in the
             Investigator's judgment.

         16. Severe heart disease (history of myocardial infarction, congestive heart disease,
             history of unstable angina pectoris, clinically significant ECG abnormality) within 6
             months prior to screening. Subjects with peripheral arterial disease will not be
             excluded if they are stable for at least 6 months prior to screening.

         17. Clinically significant vital signs, laboratory, or ECG abnormalities (eg, abnormally
             prolonged or shortened heart rate, clinical significant arrhythmias, corrected QT
             interval [QTcF] >450 ms) in the Investigator's judgement. ECG abnormalities should be
             confirmed by Investigator based on the central read results provided by the ECG core
             laboratory (Medpace Cardiovascular Core Laboratory [MCCL]).

         18. Subjects must not have an estimated glomerular filtration rate of <30 mL/min/1.73 m2,
             at screening.

         19. Impaired hepatic function, as indicated by transaminases >2 times the upper limit of
             normal or abnormalities in synthetic function tests judged by the Investigator to be
             clinically significant.

         20. Evidence of poorly-controlled diabetes (glycosylated hemoglobin >8.0%).

         21. Presence of superficial siderosis of central nervous system, or >4 cerebral
             microhemorrhages, or evidence of a prior cerebral macrohemorrhage as assessed by
             T2*-weighted gradient-recalled-echo (GRE) MRI.

         22. Presence of significant cerebral vascular pathology as assessed by MRI.

         23. Treatment with any investigational agent within 5 half-lives or 4 weeks prior to
             screening, whichever is longer.

         24. Cognitive dysfunction that might be due to past or current medication (eg,
             chemotherapy, steroids).

         25. Treatment with any biologic therapy within 5 half-lives or 3 months prior to
             screening, whichever is longer, or any subject who has been in an Alzheimer Aβ or tau
             vaccination trial unless known to have received only placebo.

         26. Treatment with anticholinergic antidepressants, typical antipsychotics, or
             barbiturates.

         27. Chronic use of opiates, opioids, or benzodiazepines:

             • Intermittent short-term use is allowed except within 5 half-lives prior to any
             neurocognitive assessment.

         28. Use or intention to use any medications/products that are cytochrome P450 (CYP)3A4
             substrates with narrow therapeutic indexes.

         29. Use or intention to use any medications/products that are known to be strong
             inducers/inhibitors of CYP3A4 within 7 days prior to the first dose and throughout the
             period of study drug administration.

         30. Consumption of grapefruit juice or grapefruit-containing products within 7 days prior
             to the first dose and throughout the period of study drug administration.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.
Subject must be at most 85 Years

Patient description (medical language): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient description (patient's own words): I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Does the patient match the trial criteria? Entailment