Posiphen® Dose-Finding, Biomarker Study in Early Alzheimer's and Parkinson's Patients

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Annovis is conducting a clinical study to investigate Posiphen in patients with Early Alzheimer's Disease (AD) and Early Parkinson's Disease (PD). Investigators are looking to recruit 68 patients in two parts of the study. In Part one of the study Investigators will recruit 14 AD and 14 PD patients who will either receive placebo (an inert pill which looks like the study drug) or the study drug Posiphen, both taken daily. In Part two of the study Investigators will recruit 40 PD patients who will receive different strengths of the study drug Posiphen taken daily. Patients will be required to come to the site for 3 face to face visits and have 4 phone calls, tests include but are not limited to, blood and CSF (spinal fluid) sampling, cognitive assessments, clinical examinations and laboratory safety tests. Primarily the Investigators are looking for the safety and tolerability of Posiphen, although Investigators will also evaluate the activity of Posiphen by a number of different biomarkers measuring pathway and target engagements.

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

Details

• Lead Sponsor: Annovis Bio Inc.
• Collaborator: Parexel
• Treatments: Phenserine

Criteria

Inclusion Criteria

Subjects must meet the following criteria:

1. Male or female aged 45 years and over.

2. Female participants must be of non-childbearing potential or 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. A) AD - CDR = 0.5 or 1. B) PD - Hoehn & Yahr ≤ 4; PD criteria by MDS-UPDRS.

5. A) AD MMSE score between the range of 18 to 28. B) PD MMSE score between the range of 18 to 30.

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

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

8. 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.

9. Stability of permitted medications prior to screening.

1. Stable for at least 12 weeks: Cholinesterase inhibitors and/or memantine medication

2. Stable for at least 4 weeks:

i. Anti-parkinsonian medication ii. Anticonvulsant medications used for epilepsy or mood stabilization; neuropathic pain indications iii. Mood-stabilizing psychotropic agents, including, but not limited to, lithium.

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

11. Good general health with no disease expected to interfere with the study.

12. Subjects previously exposed to Posiphen may be included in the study.

Exclusion Criteria

Subjects meeting any of the following criteria must not be included in the study:

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 SSRI or SNRI medication at a stable dose is acceptable.

2. History of a seizure disorder.

3. Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 450ms, or torsades de pointes.

4. Has bradycardia (<50 bpm) or tachycardia (>100 bpm) on the ECG at screening.

5. Has uncontrolled Type-1 or Type-2 diabetes . A Subject with HbA1c levels up to 7.5% can be enrolled if the investigator believes the subject's diabetes is under control.

6. Has clinically significant renal or hepatic impairment.

7. Has any clinically significant abnormal laboratory values. Subjects with liver function tests (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than twice the upper limit of normal will be excluded.

8. Is at imminent risk of self-harm, based on clinical interview and responses on the C SSRS, or of harm to others in the opinion of the Investigators. Subjects must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g. positive response to Items 4 or 5 in assessment of suicidal ideation on the C SSRS) in the past 2 months, or suicidal behavior in the past 6 months.

9. Has four or more signal hypointensities on T2*-weighted gradient recalled echo magnetic resonance sequences that are thought to represent hemosiderin deposits including microhemorrhages and superficial siderosis or evidence of acute or sub-acute micro or microhemorrhage as noted on the MRI scan.

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

11. Alcohol / Substance use disorder, moderate to severe, in the last 5 years according to the most current version DSM.

12. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 60 days prior to the start of screening. (The end of a previous investigational trial is the date the last dose of an investigational agent was taken), or five half-lives of the investigational drug, whichever is greater.

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

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

15. Subjects with learning disability or developmental delay.

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