Clinical trial: A Phase 3 Study of NE3107 in Alzheimer's Disease (NCT04669028)

Eligibility criteria:
Inclusion Criteria:

          -  1. Male or female subject aged 55 to 85 y at Screening (V1). 2. Has mild to moderate
             AD as defined by all of the following criteria:

               1. Meets the National Institute on Aging and Alzheimer's Association (NIA-AA, 2011)
                  criteria of all cause dementia and probable AD.

               2. Has a Clinical Dementia Rating (CDR) total score of 1 to 2, inclusive (mild to
                  moderate).

               3. Has an MMSE score of ≥14 and ≤24 (score is an average from Screening [V1] and
                  Baseline [V2]) with no more than a 3 point change between visits.

               4. Has an MRI of the brain that is generally supportive of AD upon local reading. A
                  CT scan can be substituted only if the subject has an absolute contraindication
                  for MRI.

               5. Has evidence of Aβ pathology based on Aβ PET scan conducted coincident with
                  diagnosis of AD or use of APTUS™ Aβ42/40 assay during the Screening Period. Scan
                  must be completed prior to randomization at V2.

                  3. Has a modified Hachinski Ischemic Scale score of ≤4 at Screening (V1). 4. If
                  taking an anticholinesterase inhibitor (AChEI) (e.g., donepezil, galantamine,
                  rivastigmine) and/or memantine at Screening (V1):

               1. Must have been taking the medication(s) for ≥3 mo and

               2. Current dose regimen and form must have remained stable for ≥6 wk prior to
                  randomization and must remain stable throughout participation in the study.

                  NOTE: Subjects not being treated with an AChEI and/or memantine at Screening (V1)
                  may also be enrolled if initiation of an AChEI and/or memantine is not planned
                  for the time period during which the subject will be participating in this study.

                  NOTE: Dosage changes during the study due to clinical deterioration should be
                  discussed with the Medical Monitor prior to being implemented.

                  5. If taking medications for glycemic control at the time of Screening (V1), must
                  be stable on the current dose regimen and form for ≥3 mo prior to randomization
                  and must remain stable throughout participation in the study.

                  6. Must meet one of the following criteria:

               1. Females: Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy, or
                  tubal ligation) for at least 6 mo prior to Screening (V1) or postmenopausal
                  (postmenopausal females must have no menstrual bleeding for at least 1 y). If
                  needed, the Investigator may confirm postmenopausal status through an FSH
                  assessment at Screening [(V1]). If not surgically sterilized or postmenopausal,
                  subject must agree to use a highly effective method of contraception that can
                  achieve a failure rate of less than 1% per year when used consistently and
                  correctly, such as hormonal contraception or a double barrier method (e.g.,
                  intrauterine device plus condom or true abstinence defined as in line with the
                  preferred and usual lifestyle of the subject) while enrolled in the study.
                  Methods of periodic abstinence (e.g., calendar, ovulation, symptothermal, post
                  ovulation) are not acceptable as noted in Section 6.8.1 of the protocol.

               2. Males: Vasectomized. If not vasectomized, must use an appropriate contraception
                  methods (e.g., double barrier or true abstinence defined as in line with the
                  preferred and usual lifestyle of the subject) while enrolled in the study.
                  Partner methods of periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post ovulation) are not acceptable as noted in Section 6.8.1 of the protocol.

                  7. Must provide voluntary written informed consent prior to Screening (V1). If
                  the subject is unable to provide informed consent due to cognitive status, the
                  subject must provide assent, and a legally authorized representative provides
                  full written informed consent on behalf of the subject.

                  8. Willing to allow collection of blood for ApoE genotyping. 9. Able to comply
                  with the study procedures, in the opinion of the Investigator.

                  10. Has a primary caregiver/study partner that has face to face contact with the
                  subject for a minimum of approximately 10 hours (h) per week spread over 2 to 5 d
                  during the week (e.g., 2 h per day for 5 d a week, or 5 h per day for 2 d a week)
                  and is willing to accept responsibility for supervising the treatment (e.g.,
                  administering study drug), accompanying the subject to clinic visits and
                  assessing the condition of the subject throughout the study in accordance with
                  all protocol requirements. The primary caregiver/study partner must be willing to
                  sign the caregiver ICF.

                  Exclusion Criteria:

          -  1. Has imaging consistent with other differential dementia diagnoses other than the
             diagnosis of AD. For example, any suggestion of vascular disease including multiple
             infarction involving large blood vessels or localized single infarction (angular
             gyrus, thalamus, anterior cerebral artery, and posterior cerebral artery region),
             multiple lacunae of the basal nuclei or white matter, or extensive lesions of the
             periventricular white matter or combination of several lesions. Additionally, any
             single lacunae in an area known to impact cognition, such as the hippocampus, will
             also be exclusionary.

             a. Should there be any evidence of neurologic symptoms between the date of the scan
             confirming diagnosis and Screening (V1), rescanning is necessary.

             2. Has abnormal laboratory tests that suggest an alternate etiology for dementia, such
             as history of uncorrected serum vitamin B12 deficiency, thyroid function abnormality,
             severe anemia, electrolyte abnormality, or history of positive syphilis serology. In
             these cases, the subject should be re evaluated to determine if these potential causes
             of dementia have been addressed. Only if these causes have been ruled out as the cause
             of the dementia, can the subject be enrolled.

             3. Diagnosis of type 1 diabetes or type 2 diabetes requiring insulin treatment.
             Subjects who become insulin dependent during the study may not continue to participate
             in the study.

             4. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure
             or loss of consciousness within 12 mo prior to Screening (V1).

             5. Has any of the following laboratory findings at Screening (V1):

               1. Alanine aminotransferase >3 × upper limit of normal (ULN), aspartate
                  aminotransferase >3 × ULN, or history of clinically significant liver disease in
                  the Investigator's medical judgment.

               2. Hemoglobin ≤10 g/dL.

               3. International normalized ratio >1.5 if not on anticoagulant medication; if the
                  subject is on anticoagulant medication, the anticoagulant medication should be
                  optimized and on a stable dose for ≥4 wk prior to Screening (V1).

               4. Creatinine clearance (Cockcroft Gault formula) of <45 mL/min.

               5. Known to be seropositive for human immunodeficiency virus (1 and 2), hepatitis B,
                  or hepatitis C. Subjects with hepatitis C who had spontaneous resolution or
                  received successful curative treatment (e.g., HARVONI® [ledipasvir/sofosbuvir])
                  with a documentation of undetectable viral load for at least 3 mo may be allowed.
                  Serological testing will not be performed as part of this study.

                  6. Female subjects who are pregnant or breastfeeding. 7. History of any medical
                  illness such as cancer requiring systemic therapy in the last 5 y, except for
                  localized basal cell carcinoma of the skin, in situ cervical cancer successfully
                  treated with surgical excision, and stable (for ≥90 d prior to Screening [V1])
                  prostate cancer.

                  8. History of severe heart failure (Grade 2 or higher on the New York Heart
                  Association scale), major stroke, uncontrolled seizure disorder, or other medical
                  illness that, in the Investigator's opinion, will increase the subject's risk of
                  participation in the study or confound study assessments.

                  9. Any surgery requiring general anesthesia that is planned to occur during the
                  study. Local anesthesia during outpatient surgery is permitted if, in the opinion
                  of the Investigator, the operation will not interfere with study procedures and
                  subject safety.

                  10. History or current evidence of major psychiatric illness such as
                  schizophrenia, bipolar disorder, or major depressive disorder that may interfere
                  with the subject's ability to perform the study and all assessments.

             a. Geriatric Depression Scale Short Form (GDS SF) score >5 at Screening (V1). NOTE:
             Mild depression or depressive mood arising in the context of AD are not criteria for
             exclusion. The use of anti epileptic medication for non seizure related treatment or
             the use of antidepressants is allowed if the dose has remained stable for ≥60 d prior
             Screening (V1).

             11. History of violent or aggressive behavior requiring medication or a formal program
             of psychosocial intervention.

             12. History of active suicidal thoughts (Type 4 or 5 on the C SSRS) in the 6 mo prior
             to Screening (V1) or at Baseline (V2), history of a suicide attempt in the previous 2
             y or >1 lifetime suicide attempt, or are at serious suicide risk, in the
             Investigator's clinical judgment.

             13. History of alcohol or drug abuse or dependence within 24 mo of Screening (V1) as
             defined by the Diagnostic and Statistical Manual of Mental Disorders 5.

               1. Positive urine screen for drugs of abuse that include methadone, cocaine, and
                  amphetamines; positive urine screen for opiates, barbiturates, or benzodiazepines
                  without a prescription.

                  14. Has participated in another Investigational New Drug research study involving
                  small molecule drugs within 60 d or biological drugs within 90 d prior to the
                  first dose of study drug in this study (Baseline [V2]) or within 5 half lives of
                  the other investigational medicinal product, whichever is longer.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 55 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