A Phase 3 Study of NE3107 in Alzheimer's Disease

• Status: Recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

U.S. multicenter, parallel group study designed to evaluate the safety and efficacy of oral 20 mg twice daily (BID) NE3107 vs placebo in 316 adult subjects with mild to moderate AD. Two coprimary outcome measures (the Alzheimer's Disease Assessment Scale Cognitive Subscale 12 [ADAS Cog12] and the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS CGIC] will be evaluated as the change from Baseline to Week 30. Secondary endpoints include measures of neuropsychological deficits, functional performance, and glycemic control. A subset of patients may volunteer for exploratory magnetic resonance imaging (volumetric changes) and positron emission tomography (cortical glucose metabolic rate) scans at baseline and week 30.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BioVie Inc.; Neurmedix Inc

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.