A Phase 3 Study of NE3107 in Probable Alzheimer's Disease

Exclusion Criteria

• •1\. Has prior brain imaging inconsistent with probable AD 2. A history of a stroke that resulted in a cognitive or motor deficit or, MRI or CT evidence of a moderate or large cerebral infarct.
• •1. Should there be any evidence of neurologic symptoms between the date of the scan confirming diagnosis and Screening (V1), rescanning is necessary.
• •3\. Has clinically relevant abnormal laboratory tests including serum vitamin B12 deficiency, thyroid function abnormality, severe anemia, or electrolyte abnormality.
• •4\. Diagnosis of type 1 diabetes or type 2 diabetes requiring insulin treatment or the need to use continuous glucose monitoring. Subjects who become insulin dependent during the study may not continue to participate in the study.
• •5\. History of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within 12 mo prior to Screening (V1).
• •6\. Subjects are ineligible, if in the opinion of the investigator, they have deficits in speech, comprehension, auditory functioning, or vision which would adversely impact their ability to perform the study's cognitive test procedures, complete rating scales, or engage in interviews.
• •7\. Has any of the following laboratory findings at Screening (V1):
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• •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.
• •8\. Female subjects with child-bearing potential (premenopausal, menstrual bleeding within the last 12 months) or who are pregnant or breastfeeding.
• •9\. 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.
• •10\. History of breast cancer. 11. 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.
• •12\. 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.
• •13\. 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.
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• •1. Geriatric Depression Scale Short Form (GDS SF) score \>8 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).
• •14\. Violent or aggressive behavior that may interfere with study participation 15. 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.
• •16\. 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.
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• •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.
• •17\. 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.
• •18\. History of Covid-19 (SARS-CoV-2) infection within 6-weeks prior to screening. Subjects with unresolved symptoms of Covid-19 infection or ongoing cognitive or other deficits attributable to post-Covid-19, that may affect participant safety or interfere with efficacy assessments, based on the Investigator's clinical judgment.