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

NCT04524351 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ANVS-12003
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Alzheimer Disease; Parkinson Disease

Keywords

Safety; Tolerability; Pharmacokinetics; Pharmacodynamics; Neurotoxic proteins; Neurotransmitters; Amyloid Precursor Proteins; Inflammatory factors; Synaptic factors; CSF

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment-Emergent Adverse Events

  Percent of patients with AEs in the Posiphen treatment arms compared to the Placebo group

  25±2 days

Secondary Outcomes (1)

• Concentration of Posiphen in Plasma

  Samples collected over a 6 hour timeframe

Other Outcomes (6)

• Change in Abeta42/Abeta40 Ratio

  Baseline to 25±2 days

• Changes in Functional Impairment

  Baseline to 25±2 days

• Changes in Functional Impairment

  Baseline to 25±2 days

Study Arms (8)

Posiphen, 80mg (Parkinson's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 80mg, taken once per day for 25±2 days.

Drug: Posiphen

Posiphen, 40mg (Parkinson's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 40mg, taken once per day for 25±2 days.

Drug: Posiphen

Posiphen, 20mg (Parkinson's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 20mg, taken once per day for 25±2 days.

Drug: Posiphen

Posiphen, 10mg (Parkinson's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 10mg, taken once per day for 25±2 days.

Drug: Posiphen

Posiphen, 5mg (Parkinson's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 5mg, taken once per day for 25±2 days.

Drug: Posiphen

Placebo (Parkinson's Participants)

PLACEBO COMPARATOR

Placebo Oral Capsule, taken once per day for 25±2 days.

Drug: Placebo

Placebo (Alzheimer's Participants)

PLACEBO COMPARATOR

Placebo Oral Capsule, taken once per day for 25±2 days.

Drug: Placebo

Posiphen, 80mg (Alzheimer's Participants)

ACTIVE COMPARATOR

Posiphen Oral Capsule, 80mg, taken once per day for 25±2 days.

Drug: Posiphen

Interventions

Posiphen DRUG

Solid oral dosage form, capsule

Posiphen, 10mg (Parkinson's Participants); Posiphen, 20mg (Parkinson's Participants); Posiphen, 40mg (Parkinson's Participants); Posiphen, 5mg (Parkinson's Participants); Posiphen, 80mg (Alzheimer's Participants); Posiphen, 80mg (Parkinson's Participants)

Placebo DRUG

Solid oral dosage form, capsule

Placebo (Alzheimer's Participants); Placebo (Parkinson's Participants)

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet the following criteria:
• Male or female aged 45 years and over.
• 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.
• Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
• A) AD - CDR = 0.5 or 1. B) PD - Hoehn \& Yahr ≤ 4; PD criteria by MDS-UPDRS.
• A) AD MMSE score between the range of 18 to 28. B) PD MMSE score between the range of 18 to 30.
• General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.
• No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
• 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.
• Stability of permitted medications prior to screening.
• Stable for at least 12 weeks: Cholinesterase inhibitors and/or memantine medication
• 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.
• Adequate visual and hearing ability (physical ability to perform all the study assessments).
• Good general health with no disease expected to interfere with the study.

You may not qualify if:

• Subjects meeting any of the following criteria must not be included in the study:
• 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.
• History of a seizure disorder.
• Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 450ms, or torsades de pointes.
• Has bradycardia (\<50 bpm) or tachycardia (\>100 bpm) on the ECG at screening.
• 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.
• Has clinically significant renal or hepatic impairment.
• 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.
• 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.
• 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.
• 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).
• Alcohol / Substance use disorder, moderate to severe, in the last 5 years according to the most current version DSM.
• 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.
• Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.
• History of lumbar spine surgery or chronic low back pain (CLBP).

Sponsors & Collaborators

• Annovis Bio Inc.: lead
• Parexel: collaborator

Study Sites (13)

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Homestead Associates in Research

Miami, Florida, 33032, United States

Location

Ezy Medical Research Co.

Miami, Florida, 33175, United States

Location

Conquest Research LLC

Winter Park, Florida, 32789, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

North Suffolk Neurology, PC

Port Jefferson Station, New York, 11776, United States

Location

Penn Medicine, Department of Neurology, U of PA

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Aspen Clinical Research LLC

Orem, Utah, 84058, United States

Location

Related Publications (1)

• Fang C, Hernandez P, Liow K, Damiano E, Zetterberg H, Blennow K, Feng D, Chen M, Maccecchini M. Buntanetap, a Novel Translational Inhibitor of Multiple Neurotoxic Proteins, Proves to Be Safe and Promising in Both Alzheimer's and Parkinson's Patients. J Prev Alzheimers Dis. 2023;10(1):25-33. doi: 10.14283/jpad.2022.84.

  PMID: 36641607 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Parkinson Disease

Interventions

phenserine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Results Point of Contact

• Title: Maria Maccecchini, PhD, CEO
• Organization: Annovis Bio

maccecchini@annovisbio.com

(610) 727-3710

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 24, 2020
• Study Start: August 14, 2020
• Primary Completion: August 16, 2021
• Study Completion: January 31, 2022
• Last Updated: February 28, 2023
• Results First Posted: February 28, 2023

Record last verified: 2023-02

Locations

US (13)