A Dose-ranging Study to Investigate Efficacy of Buntanetap in Mild to Moderate AD

NCT05686044 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ANVS -22002
• Study Type: interventional
• Target: 351
• Locations: 1 country
• Sites: 54

Brief Summary

The purpose of this study is to measure efficacy and safety of three different doses of buntanetap/Posiphen compared with placebo in participants with mild to moderate Alzheimer's disease. Study details include: The double-blind treatment duration will include a screening period of up to 42 days followed by 12 weeks of treatment at home. The study duration will be 4-5 months. There will be 4 in-clinic visits and 1 phone call.

Conditions

Alzheimer Disease

Keywords

Alzheimer

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Week 12 in ADAS-Cog11

  Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) measures cognitive functions and non-cognitive functions such as mood and behavior. It was designed to measure the cognitive and behavioral domains known to be affected in Alzheimer disease, including memory, language, orientation, construction, and planning of simple designs, and completed simple goal-oriented behaviors. Specifically, the ADAS-Cog comprises ratings from 11 components: word recall, word recognition, constructional praxis, orientation, naming objects and fingers, commands, ideational praxis, remembering test instructions, spoken language, word finding, and comprehension. Total scores range from 0-70, with higher scores indicating greater cognitive impairment.

  Baseline to the end of treatment period (12 weeks)

• ADCS-CGIC at Week 12

  Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the patient and interview of informants. The ADCS-CGIC measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination of the patient and an interview of the study partner. A skilled and experienced clinician who is blinded to treatment assignment rates the patient on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). Lower scores indicate better improvement.

  Baseline to the end of treatment period (12 weeks)

Secondary Outcomes (1)

• Change From Baseline to Week 12 in ADCS-ADL

  Baseline to end of treatment period (12 weeks)

Other Outcomes (1)

• Change From Baseline to Week 12 in Plasma Biomarkers

  Baseline to the end of treatment period (12 weeks)

Study Arms (4)

7.5mg Buntanetap/Posiphen

EXPERIMENTAL

Buntanetap/Posiphen 7.5mg oral capsule with daily administration for a period of 12 weeks

Drug: Buntanetap/Posiphen

15mg Buntanetap/Posiphen

EXPERIMENTAL

Buntanetap/Posiphen 15mg oral capsule with daily administration for a period of 12 weeks

Drug: Buntanetap/Posiphen

30mg Buntanetap/Posiphen

EXPERIMENTAL

Buntanetap/Posiphen 30mg oral capsule with daily administration for a period of 12 weeks

Drug: Buntanetap/Posiphen

Placebo

PLACEBO COMPARATOR

Placebo oral capsule with daily administration for a period of 12 weeks

Drug: Placebo

Interventions

Buntanetap/Posiphen DRUG

HPMC (vegetarian source) capsule shells

Also known as: Posiphen Tartrate

15mg Buntanetap/Posiphen; 30mg Buntanetap/Posiphen; 7.5mg Buntanetap/Posiphen

Placebo DRUG

HPMC (vegetarian source) capsule shells

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Alzheimer's disease according to National Institute on Aging and National Institute on Aging and Alzheimer's Association criteria for probable AD
• Male or female aged 55 - 85 years.
• MMSE 14-24.
• Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to study visits at designated times.
• Female participants of childbearing potential\* must have a negative urine pregnancy test at Screening, must be non-lactating and must agree to use a highly effective method of contraception (i.e., a method resulting in a failure rate of less than 1% per year when used consistently and correctly) during the trial and for 4 weeks after the last dose of trial treatment, such as:
• Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation
• Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner (a vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the participant, and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used)
• Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be in relation to the duration of the study and the preferred and usual lifestyle of the participant) \*Non-childbearing potential includes surgically sterilized or postmenopausal with no menstrual bleeding for at least one year prior to study start.
• Male participants must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subject must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:
• Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation
• Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation

You may not qualify if:

• 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 selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) medication at a stable dose is acceptable.
• Has non-AD dementia, such as vascular dementia, Lewy body dementia, frontotemporal disease, Parkinson disease dementia, B12 and thyroid deficiency caused dementia.
• History of a seizure disorder, if stable on medication is acceptable.
• Has a history or current evidence of long QT syndrome, Fridericia's formula corrected QT (QTcF) interval ≥ 450 ms for men and 460 ms for women, 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 (CKD-EPI with normal \<60 mL/min/BSA (body surface area) or hepatic impairment (ALP \> 2.0 ULN and/or total bilirubin \> 2.0 ULN) .
• Has any clinically significant abnormal laboratory values. Participants 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. Participants 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 cancer or has had a malignant tumor within the past year, except participants who underwent potentially curative therapy with no evidence of recurrence. (Participants 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 4 weeks prior to the start of screening, or five half-lives of the investigational drug, whichever is greater.
• The end of a previous investigational trial is the date the last dose of an investigational agent was taken.
• Participants with learning disability or developmental delay.
• Participants whom the site PI deems to be otherwise ineligible.

Sponsors & Collaborators

• Annovis Bio Inc.: lead

Study Sites (54)

CCT Research - Gilbert Neurology Partners

Gilbert, Arizona, 85297, United States

Location

CCT Research - Foothills Center

Phoenix, Arizona, 85004, United States

Location

The Belinga Clinic

Fort Smith, Arkansas, 72916, United States

Location

Sun Valley Research Center

Imperial, California, 92251, United States

Location

CenExel Clinical Clinical Research, Inc

Los Alamitos, California, 90720, United States

Location

Cenexel Rocky Mountain Clinical Research

Englewood, Colorado, 80113, United States

Location

Ki Health Partners LLC D/B/A New England Institute for Clinical Research

Stamford, Connecticut, 06824, United States

Location

Visionary Investigators Network

Aventura, Florida, 33180, United States

Location

K2 Medical Research

Clermont, Florida, 34711, United States

Location

The Neurology Institute - Coral Springs

Coral Springs, Florida, 33067-4640, United States

Location

JY Research Inst.

Cutler Bay, Florida, 33189, United States

Location

Arrow Clinical trial

Daytona Beach, Florida, 32114, United States

Location

Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

New Life Medical Research Center

Hialeah, Florida, 33012, United States

Location

CenExel RCA

Hollywood, Florida, 33024, United States

Location

Coral Clinic Reserach LLC

Homestead, Florida, 33032, United States

Location

Charter Research

Lady Lake, Florida, 32159, United States

Location

ClinCloud, LLC

Maitland, Florida, 32751, United States

Location

K2 Medical Research

Maitland, Florida, 32751, United States

Location

Merritt Island Clinical Research LLC

Merritt Island, Florida, 32952, United States

Location

Premier Clinical Research Institute, Inc

Miami, Florida, 33122, United States

Location

Gold Coast Health Research, LLC

Miami, Florida, 33155, United States

Location

Medical Professional Clinical Research Center, Inc

Miami, Florida, 33165, United States

Location

Reliant Medical Research

Miami, Florida, 33165, United States

Location

Ezy Medical Research Co.

Miami, Florida, 33175, United States

Location

Nuovida Research Center

Miami, Florida, 33186, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Visionary Investigators Network

Pembroke Pines, Florida, 33026, United States

Location

Napa Research

Pompano Beach, Florida, 33064, United States

Location

K2 Medical Research

Tampa, Florida, 33067, United States

Location

K2 Summit Research

The Villages, Florida, 32159, United States

Location

ClinCloud, LLC

Viera, Florida, 32940, United States

Location

Conquest Research, LLC

Winter Park, Florida, 32789, United States

Location

Charter Research

Winter Park, Florida, 32792, United States

Location

CenExel iResearch, LLC

Decatur, Georgia, 30030, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

Hawaii Pacific Neuroscience, LLC

Honolulu, Hawaii, 96817, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Josephson Wallack Munshower Neurology, P.C.

Indianapolis, Indiana, 46256, United States

Location

Northern Light Acadia Hospital

Bangor, Maine, 04401, United States

Location

MedVadis Research

Waltham, Massachusetts, 02451, United States

Location

Quest Research Institue

Farmington Hills, Michigan, 48334, United States

Location

Insight Research Institute

Flint, Michigan, 48507, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

CenExel Clinical Research, Inc

Toms River, New Jersey, 08755, United States

Location

Velocity Clinical Research

Syracuse, New York, 13057, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Neuroscience Centre (CINAC)

Canton, Ohio, 44718, United States

Location

Dayton Center for Neurological Disorders, Inc

Centerville, Ohio, 45459, United States

Location

NeuroCare Plus

Houston, Texas, 77094, United States

Location

Be Well Clinical Studies, LLC

Round Rock, Texas, 78681, United States

Location

Central Texas Neurology Consultants

Round Rock, Texas, 78681, United States

Location

Inland Northwest Research

Spokane, Washington, 99202-1342, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

phenserine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Matthew Peterson, PhD
• Organization: Annovis Bio, Inc.

peterson@annovisbio.com

484-875-3192

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 17, 2023
• Study Start: April 1, 2023
• Primary Completion: February 13, 2024
• Study Completion: February 13, 2024
• Last Updated: April 29, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-04

Locations

US (54)