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Alzheimer DiseasePhase 2/3NCT05686044

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

A Phase 2/3 study testing Buntanetap/Posiphen in people with Alzheimer Disease, run by Annovis Bio Inc. at 54 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Buntanetap/Posiphen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
351 participants
Where
54 sitesUnited States
Study dates
1 Apr 2023to 13 Feb 2024
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Participants can provide written informed consent. If PI deems that participant cannot fully understand the consent form to give consent, their legally authorized representative (LARs) can provide written informed consent. Participants can comply with scheduled visits, and other study-related procedures to complete the study with the help of the study partner.
  • No evidence of current suicidal ideation or previous suicide attempt in the past 2 months as evaluated in the Columbia Suicide Severity Rating Scale nor suicidal behavior in the past 6 months as per investigator.
  • Stability of permitted medications for at least 4 weeks prior to screening.
  • Cholinesterase inhibitors and/or memantine medication
  • Anticonvulsant medications used for epilepsy or mood stabilization, neuropathic pain indications.
  • Mood-stabilizing psychotropic agents, including, but not limited to, lithium.
  • Adequate visual and hearing ability (physical ability to perform all the study assessments) as per investigator.
  • Good general health with no disease expected to interfere with the study as per investigator.

Who cannot join

  • 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.
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  • 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.
  • Participants with a known allergy to the investigational drug or any of its components. Here are all the inactive ingredients of the investigational medicinal product:
  • Silicified Microcrystalline Cellulose
  • Dibasic Calcium Phosphate Dihydrate
  • Mannitol
  • Magnesium Stearate
  • Hypromellose (capsule shells structure)
  • titanium dioxide (opacifier of the capsule shells)
  • Subject is currently pregnant, breast-feeding and/or lactating.
  • Subject is currently taking strong and moderate CYP3A4 inhibitors and/or inducers. (e.g., CYP3A4 inhibitors Itraconazole, Ketoconazole, Azamulin, Troleandomycin, Verapamil; CYP3A4 inducers Rifampicin)

Trial locations and contacts

54 sites in 1 country.

54 sites in 1 country

United States54 sites

  • Visionary Investigators Network

    Aventura, Florida, 33180

  • Northern Light Acadia Hospital

    Bangor, Maine, 04401

  • Hassman Research Institute

    Berlin, New Jersey, 08009

  • Neuroscience Centre (CINAC)

    Canton, Ohio, 44718

  • Dayton Center for Neurological Disorders, Inc

    Centerville, Ohio, 45459

  • K2 Medical Research

    Clermont, Florida, 34711

  • The Neurology Institute - Coral Springs

    Coral Springs, Florida, 33067-4640

  • JY Research Inst.

    Cutler Bay, Florida, 33189

  • Arrow Clinical trial

    Daytona Beach, Florida, 32114

  • CenExel iResearch, LLC

    Decatur, Georgia, 30030

  • Accel Research Sites - DeLand Clinical Research Unit

    DeLand, Florida, 32720

  • Duke University

    Durham, North Carolina, 27705

  • Cenexel Rocky Mountain Clinical Research

    Englewood, Colorado, 80113

  • Quest Research Institue

    Farmington Hills, Michigan, 48334

  • Insight Research Institute

    Flint, Michigan, 48507

  • The Belinga Clinic

    Fort Smith, Arkansas, 72916

  • Center for Advanced Research & Education

    Gainesville, Georgia, 30501

  • CCT Research - Gilbert Neurology Partners

    Gilbert, Arizona, 85297

  • New Life Medical Research Center

    Hialeah, Florida, 33012

  • CenExel RCA

    Hollywood, Florida, 33024

  • Coral Clinic Reserach LLC

    Homestead, Florida, 33032

  • Hawaii Pacific Neuroscience, LLC

    Honolulu, Hawaii, 96817

  • NeuroCare Plus

    Houston, Texas, 77094

  • Sun Valley Research Center

    Imperial, California, 92251

  • Josephson Wallack Munshower Neurology, P.C.

    Indianapolis, Indiana, 46256

  • Charter Research

    Lady Lake, Florida, 32159

  • CenExel Clinical Clinical Research, Inc

    Los Alamitos, California, 90720

  • ClinCloud, LLC

    Maitland, Florida, 32751

  • K2 Medical Research

    Maitland, Florida, 32751

  • Merritt Island Clinical Research LLC

    Merritt Island, Florida, 32952

  • Premier Clinical Research Institute, Inc

    Miami, Florida, 33122

  • Gold Coast Health Research, LLC

    Miami, Florida, 33155

  • Medical Professional Clinical Research Center, Inc

    Miami, Florida, 33165

  • Reliant Medical Research

    Miami, Florida, 33165

  • Ezy Medical Research Co.

    Miami, Florida, 33175

  • Nuovida Research Center

    Miami, Florida, 33186

  • Renstar Medical Research

    Ocala, Florida, 34470

  • Visionary Investigators Network

    Pembroke Pines, Florida, 33026

  • CCT Research - Foothills Center

    Phoenix, Arizona, 85004

  • Napa Research

    Pompano Beach, Florida, 33064

  • Be Well Clinical Studies, LLC

    Round Rock, Texas, 78681

  • Central Texas Neurology Consultants

    Round Rock, Texas, 78681

  • Inland Northwest Research

    Spokane, Washington, 99202-1342

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

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

    Stamford, Connecticut, 06824

  • Velocity Clinical Research

    Syracuse, New York, 13057

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • K2 Medical Research

    Tampa, Florida, 33067

  • K2 Summit Research

    The Villages, Florida, 32159

  • CenExel Clinical Research, Inc

    Toms River, New Jersey, 08755

  • ClinCloud, LLC

    Viera, Florida, 32940

  • MedVadis Research

    Waltham, Massachusetts, 02451

  • Conquest Research, LLC

    Winter Park, Florida, 32789

  • Charter Research

    Winter Park, Florida, 32792

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Multicenter Study of Buntanetap in Participants With Mild to Moderate Alzheimer's Disease

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.

Read the detailed description

320 mild to moderate AD participants will be randomized to 7.5 mg, 15 mg, 30mg of buntanetap/Posiphen once daily (QD) or placebo. If they provide informed consent, they will undergo a Screening Visit, and if they are considered eligible per the inclusion and exclusion criteria, they will proceed to participate in the treatment period. Randomized participants will visit the clinic for the first-time dosing in clinic, followed by an at home dosing period of 12 weeks, with daily administration of 7.5 mg, 15 mg or 30 mg of buntanetap/Posiphen or placebo. Participants will be required to visit clinics Day 0 (baseline), 6 weeks, and 12 weeks (end-of-trial), where they 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) and psychometric tests (Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-ADL), Digital Symbol Substitution Test (DSST), Mini Mental State Examination (MMSE)). At the end of blood sampling, the participants will need to stay for a minimum of 1 hour of observation. After all end-of-study procedures are complete, the subject will be discharged to home. A 24-hour follow-up call will occur after all clinical visits to assess the participants current condition and if there are any additional adverse events or questions.

The study will be a 12-weeks, placebo-controlled and double-blind trial: participants, investigators and the sponsor will be blinded to the participants' treatment.

Qualified participants will be randomly assigned at a 1:1:1:1 ratio to one of the four treatment arms: buntanetap/Posiphen 7.5 mg, buntanetap/Posiphen 15 mg, buntanetap/Posiphen 30mg, and placebo, through an Interactive Randomization System, after a screening period of up to 42 days.

ADAS-Cog 11, ADCS-CGIC, ADCS-ADL, DSST, and MMSE will be assessed by clinicians who have successfully completed the requisite certifications/trainings for each assessment.

One interim analysis is planned. It will take place when 90 enrolled subjects (~30%) have completed the Week 6 assessments to re-assess the sample size. No interim analyses are planned for the purpose of stopping the study early for futility.

Being tested
Buntanetap/Posiphen, Placebo
Keywords
Alzheimer
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Buntanetap/PosiphenDrug

    Also called Posiphen Tartrate

    HPMC (vegetarian source) capsule shells

  • PlaceboDrug

    HPMC (vegetarian source) capsule shells

Study groups in NCT05686044
Study groupRoleWhat they receive
7.5mg Buntanetap/PosiphenExperimentalBuntanetap/Posiphen 7.5mg oral capsule with daily administration for a period of 12 weeks
Receives: Drug: Buntanetap/Posiphen
15mg Buntanetap/PosiphenExperimentalBuntanetap/Posiphen 15mg oral capsule with daily administration for a period of 12 weeks
Receives: Drug: Buntanetap/Posiphen
30mg Buntanetap/PosiphenExperimentalBuntanetap/Posiphen 30mg oral capsule with daily administration for a period of 12 weeks
Receives: Drug: Buntanetap/Posiphen
PlaceboPlacebo comparatorPlacebo oral capsule with daily administration for a period of 12 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to the end of treatment period (12 weeks)

  2. 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.

    Measured: Baseline to the end of treatment period (12 weeks)

Secondary outcomes (1)

  1. Change From Baseline to Week 12 in ADCS-ADL

    Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-ADL) is a 23-item inventory scale developed as a rater-administered questionnaire answered by the participant's study partner.

    The ADCS-ADL measures 6 basic activities of daily living (BADL) items and 17 instrumental activities of daily living (IADL) items that provide a total score from 0-78, with a lower score indicating greater severity. Basic activities include basic self-care tasks such as feeding, mobility, toileting, bathing, grooming and dressing. Instrumental activities are more complex and vary based on cultural norms, gender roles. As such, instrumental activities tend to include a broad range of activities.

    Caregivers are asked to rate the degree to which their family member or loved one can perform a variety of tasks. The assessed activities provide a total score from 0-78. Participants with a lower score indicates greater severity.

    Measured: Baseline to end of treatment period (12 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2023
  2. Study start1 Apr 2023
  3. Primary completion13 Feb 2024
  4. Study completion13 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
351 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05686044
Sponsor's protocol ID
ANVS -22002
Status last verified
Apr 2025
First submitted
6 Jan 2023
Last updated
29 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Buntanetap/Posiphen in people with Alzheimer Disease, run by Annovis Bio Inc. at 54 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 12 in ADAS-Cog11 (time frame: Baseline to the end of treatment period (12 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05686044.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.

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