Safety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with early Alzheimer's disease (AD).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Annovis Bio Inc.; QR Pharma Inc.
• Collaborator: Alzheimer's Disease Cooperative Study (ADCS)
• Treatments: Phenserine; Physostigmine

Criteria

Inclusion Criteria:

1. Male or female aged 55 to 85 years (inclusive).

2. Female participants 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.

3. Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.

4. Diagnosis of amnestic MCI or probable mild AD according to the core clinical criteria outlined in the NIA-AA Guidelines.

5. MMSE score between the range of 21 to 27.

6. CDR score of 0.5 or 1.0.

7. A score on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised within the following education-adjusted ranges:

• Less than or equal to 11 for 16 or more years of education

• Less than or equal to 9 for 8-15 years of education

• Less than or equal to 6 for 0-7 years of education

8. To qualify for entry, subjects will have CSF Aβ42 levels that are consistent with Alzheimer's disease as measured via mass spectrometry by C2N.

9. General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.

10. A minimum of 6 years of education or good work history.

11. Study partner is available who has frequent contact with the subject (e.g. average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject. Study partner (or other individual) should also oversee study drug administration if needed to ensure compliance with dose regimen.

12. No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.

13. MRI scan within the 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Lacunes that are not believed to contribute to the subject's cognitive impairment are permissible. If there is no MRI available within a 12-month timeframe, then an MRI must be performed as part of the screening procedures for eligibility.

14. Stability of permitted medications for 4 weeks prior to baseline. NOTE: Cholinesterase inhibitors and or memantine are allowable only if stable for 12 weeks prior to screen. If taking Aricept (donepezil), no more than 10 mg/day is permitted during the course of the study.

15. Adequate visual and hearing ability (physical ability to perform all the study assessments).

16. Good general health with no disease expected to interfere with the study. Subjects may have common age-related disorders (i.e., hypertension, type II diabetes, dyslipidemia, and hypothyroidism) as long as these disorders are being controlled by diet or medication.

17. Must speak English fluently.

Exclusion Criteria:

1. Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or history of depression that is stable on treatment with a tricyclic antidepressant SSRI or SNRI medication at a stable dose is acceptable.

2. Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumor.

3. Dementia other than AD, such as Acquired Immunodeficiency Syndrome (AIDS), Creutzfeldt-Jakob disease (CJD), Lewy Bodies dementia (LBD), Cerebrovascular dementia (CVD), Progressive Supranuclear Palsy (PSP), or normal pressure hydrocephalus (NPH).

4. History of a seizure disorder.

5. Clinically significant abnormalities in screening laboratory or ECG results.

6. Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, makes them ineligible for participation in this study.

7. Has four or more microinfarcts as noted in the MRI scan.

8. Has cancer or has had a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence. (Patients with stable untreated prostate cancer or skin cancers are not excluded).

9. According to the criteria of the most current version of the DSM, alcohol abuse, alcohol dependence, or drug abuse in the past 5 years.

10. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 16 weeks prior to screening. (The end of a previous investigational trial is the date the last dose of an investigational agent was taken).

11. Resides in a skilled nursing facility.

12. Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.

13. History of lumbar spine surgery or chronic low back pain (CLBP).

14. Subjects whom the site PI deems to be otherwise ineligible.