Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04524351
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : January 12, 2021
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Annovis Bio Inc.

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Parkinson Disease Drug: Posiphen Phase 1 Phase 2

Detailed Description:

Part 1 is a study with 14 Early AD and 14 Early PD patients who are randomized to 80 mg of Posiphen or placebo. Participants will undergo a Screening Visit, provide informed consent and be evaluated for eligibility per the inclusion and exclusion criteria. If enrolled, participants will proceed to the randomized treatment portions of the study. Period 1 consists of first-time dosing in clinic with administration of 80 mg of Posiphen or Placebo. Period 2 consists of an at home dosing period of 25±2 days, with daily administration of 80 mg of Posiphen or Placebo. Period 3 will be comprised of a stay at the clinical research unit where the subject will undergo study procedures that include safety assessments (AE and concomitant medication monitoring, 12-lead ECGs, clinical laboratory testing, vital signs assessments, and physical examinations), the last dose of Posiphen or Placebo, and 6 hours of blood and CSF sampling. At the end of blood/CSF sampling, the subjects will need to stay for a minimum of 1 hour of observation but may stay if necessary for observation until the following day (e.g., if the subject has blood/CSF sampling on Day 25, he/she may stay for observation until Day 26). After all end-of-study procedures are complete, the subject will be discharged to home. A 24-hour follow-up call will occur to assess the participants current condition and if there are any additional adverse events to report.

After completion of Part 1 of the study, the plasma and CSF samples will be analyzed for the biomarkers to determine if changes are needed to the biomarkers to be measured in Part 2. Since the conduct of the study in Part 2 will be identical to the conduct of the study in Part 1, recruitment will continue uninterrupted. The only potential change between Part 1 and Part 2 are the biomarkers to be measured.

Part 2 is a study with 40 Early PD patients, 10 patients each who are randomized to one of 4 treatment conditions of Posiphen (5 mg, 10 mg, 20 mg, or 40 mg). Participants will undergo a Screening Visit, provide informed consent and be evaluated for eligibility per the inclusion and exclusion criteria. If enrolled, participants will proceed to the randomized treatment portions of the study. Period 1 consists of first-time dosing in clinic with administration of 5, 10, 20, or 40mg of Posiphen. Period 2 consists of an at home dosing period of 25±2 days, with daily administration of 5, 10, 20, or 40mg of Posiphen. Period 3 will be comprised of a stay at the clinical research unit where the subject will undergo study procedures that include safety assessments (AE and concomitant medication monitoring, 12-lead ECGs, clinical laboratory testing, vital signs assessments, and physical examinations), the last dose of Posiphen or Placebo, and 6 hours of blood and CSF sampling. At the end of blood/CSF sampling, the subject will need to stay for a minimum of 1 hour of observation but may stay if necessary for observation until the following day (e.g., if the subject has blood/CSF sampling on Day 25, he/she may stay for observation until Day 26). After all end-of-study procedures are complete, the subject will be discharged to home. A 24-hour follow-up call will occur to assess the participant's current condition and if there are any additional adverse events to report.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD) or Early Parkinson's Disease (PD)
Actual Study Start Date : August 14, 2020
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2021


Arm Intervention/treatment
Active Comparator: Posiphen, 80mg
Posiphen Oral Capsule, 80mg, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule

Active Comparator: Posiphen, 40mg
Posiphen Oral Capsule, 40mg, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule

Active Comparator: Posiphen, 20mg
Posiphen Oral Capsule, 20mg, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule

Active Comparator: Posiphen, 10mg
Posiphen Oral Capsule, 10mg, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule

Active Comparator: Posiphen, 5mg
Posiphen Oral Capsule, 5mg, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule

Placebo Comparator: Placebo
Placebo Oral Capsule, taken once per day for 25±2 days.
Drug: Posiphen
Solid oral dosage form, capsule




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 25±2 days ]
    Percent of patients with AEs in the Posiphen treatment arms compared to the Placebo group


Secondary Outcome Measures :
  1. Concentration of Posiphen in Plasma [ Time Frame: 6 hours ]
    Plasma measurements of Posiphen to be reported as ng/mL over the 6 hours of sampling.


Other Outcome Measures:
  1. Changes in Functional Impairment [ Time Frame: Baseline to 25±2 days ]
    Functional impairment will be evaluated using the Clinical Dementia Rating (CDR) scale (Berg1988) for AD.

  2. Changes in Functional Impairment [ Time Frame: Baseline to 25±2 days ]
    Functional impairment will be evaluated using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scale (Goetz 2008) for those with PD.

  3. Changes in Cognition [ Time Frame: Baseline to 25±2 days ]
    For both populations, the Mini-Mental State Examination (MMSE) scale (Folstein 1975) will be administered as a global measure of cognition.

  4. Changes in Cognition [ Time Frame: Baseline to 25±2 days ]
    For both populations, the Coding subtest from the Weschler Adult Intelligence Scales, 4th edition (WAIS-IV) will serve as a sensitive measure of CNS dysfunction.

  5. Changes in Cognition [ Time Frame: Baseline to 25±2 days ]
    The subjects with AD will also be administered the The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) Subscale (Schafer 2012).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04524351


Contacts
Layout table for location contacts
Contact: Nathan Chadwick +44 (0) 189 581 8969 nathan.chadwick@parexel.com

Locations
Layout table for location information
United States, Florida
MD Clinical Recruiting
Hallandale Beach, Florida, United States, 33009
Contact: William Torres    954-455-5757    feasibility@velocityclinical.com   
Principal Investigator: Beth E Safirstein, MD         
Homestead Associates in Research Recruiting
Miami, Florida, United States, 33032
Contact: Mabel Perez    305-246-0873    mperez@associatesinresearch.com   
Principal Investigator: Angel M Carrasco, MD         
Ezy Medical Research Co. Recruiting
Miami, Florida, United States, 33175
Contact: Manuel F Fernandez, MD    786-483-8162    manffernandez@gmail.com   
Conquest Research LLC Recruiting
Winter Park, Florida, United States, 32789
Contact: Rekha Gandhi, MD    407-916-0060    info@conquestresearch.com   
Principal Investigator: Rekha Gandhi, MD         
United States, Hawaii
Hawaii Pacific Neuroscience Recruiting
Honolulu, Hawaii, United States, 96817
Contact: Catherine Mitchell    808-564-6141    cmitchell@hawaiineuroscience.com   
Principal Investigator: Kore Liow, MD         
United States, Michigan
Quest Research Institute Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Heather Fasczewski    248-957-8940    heather@questri.com   
Principal Investigator: Aaron Ellenbogen, DO         
United States, Texas
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Sudha Seshadri, MD    210-567-8229    Seshadri@uthscsa.edu   
United States, Utah
Aspen Clinical Research LLC Recruiting
Orem, Utah, United States, 84058
Contact: Kaislee Ferris    801-356-5555    recruiters@aspclinic.com   
Principal Investigator: Jason L Andersen, DO         
Sponsors and Collaborators
Annovis Bio Inc.
Parexel
Layout table for additonal information
Responsible Party: Annovis Bio Inc.
ClinicalTrials.gov Identifier: NCT04524351    
Other Study ID Numbers: ANVS-12003
First Posted: August 24, 2020    Key Record Dates
Last Update Posted: January 12, 2021
Last Verified: January 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Annovis Bio Inc.:
Safety
Tolerability
Pharmacokinetics
Pharmacodynamics
Neurotoxic proteins
Neurotransmitters
Amyloid Precursor Proteins
Inflammatory factors
Synaptic factors
CSF
Additional relevant MeSH terms:
Layout table for MeSH terms
Parkinson Disease
Alzheimer Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Dementia
Tauopathies
Phenserine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs