Buntanetap for Alzheimer's Disease

No longer recruiting at 60 trial locations

Overseen By Peter McAllister, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Annovis Bio Inc.

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Schizophrenia, Bipolar, Major depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called buntanetap for individuals with mild to moderate Alzheimer's disease, a condition that affects memory and thinking. Participants will receive one of three doses of the drug or a placebo (a pill with no active medicine) to determine the most effective dose. The trial lasts about 4-5 months, with most treatment occurring at home. Ideal candidates have a confirmed Alzheimer's diagnosis and experience memory problems that affect daily life. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval. Participants have the opportunity to contribute to potentially groundbreaking advancements in Alzheimer's treatment.

Do I need to stop my current medications to join the trial?

The trial requires that your current medications be stable for at least 4 weeks before screening. You may need to stop taking strong and moderate CYP3A4 inhibitors or inducers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that buntanetap, also known as Posiphen, is safe and well-tolerated. Studies have found that doses up to 80 mg per day are safe for those with Alzheimer's and Parkinson's diseases. The current trial tests doses of 7.5 mg, 15 mg, and 30 mg, which are lower than the safe levels identified in earlier studies.

Participants in these studies did not experience major side effects at these doses, indicating that the treatment is generally well-tolerated and causes little discomfort or harm. While all treatments can have some side effects, buntanetap has been shown to be generally safe for people with similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for Alzheimer's disease, like donepezil or memantine, work by boosting neurotransmitters in the brain. But Buntanetap works differently, targeting the production of proteins that are thought to contribute to nerve cell damage in Alzheimer's. This unique approach could potentially slow down the progression of the disease rather than just alleviating symptoms. Researchers are excited about Buntanetap because it offers a fresh strategy for tackling Alzheimer's, with the possibility of more effective long-term outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research has shown that buntanetap may help treat Alzheimer's disease. In earlier studies, patients with mild Alzheimer's who took buntanetap showed noticeable improvements in thinking, memory, and understanding. The best results appeared with the highest dose tested, 30 mg. In this trial, participants will receive different doses of buntanetap—7.5 mg, 15 mg, and 30 mg—or a placebo. The treatment was generally well tolerated, with most people not experiencing serious side effects. These findings suggest that buntanetap could be a helpful option for managing Alzheimer's symptoms. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for people aged 55-85 with mild to moderate Alzheimer's, as per NIA criteria. They must have a study partner, be in good health without diseases affecting the study, and not at risk of self-harm. Women of childbearing age need a negative pregnancy test and agree to contraception; men must also agree to contraceptive measures.

Inclusion Criteria

Adequate visual and hearing ability (physical ability to perform all the study assessments) as per investigator.

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.

Participants can provide written informed consent. If PI deems that participant cannot fully understand ICF 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.

Exclusion Criteria

Subject is currently pregnant, breast-feeding and/or lactating.

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).

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

1 visit (in-person)

Treatment

Participants receive daily administration of buntanetap/Posiphen or placebo for 12 weeks, with in-clinic visits for safety assessments and psychometric tests

12 weeks

3 visits (in-person), 1 phone call

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 phone call

What Are the Treatments Tested in This Trial?

Interventions

• Buntanetap
• Placebo

Trial Overview The trial tests Buntanetap's effectiveness and safety against a placebo in those with Alzheimer's over 12 weeks at home. Participants will undergo screening for up to 42 days before treatment starts, followed by four clinic visits and one phone call over approximately five months.

How Is the Trial Designed?

Group I: 7.5mg Buntanetap/Posiphen Experimental Treatment 1 Intervention

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

Group II: 30mg Buntanetap/Posiphen Experimental Treatment 1 Intervention

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

Group III: 15mg Buntanetap/Posiphen Experimental Treatment 1 Intervention

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

Group IV: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Annovis Bio Inc.

Lead Sponsor

Trials

6

Recruited

1,700+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36641607/

Buntanetap, a Novel Translational Inhibitor of Multiple ... Conclusions: Buntanetap is well tolerated and safe at doses up to 80mg QD in both AD and PD patients. Cmax and AUC increase with dose without evidence for a ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724002462

Buntanetap, a Novel Translational Inhibitor of Multiple ... Despite the small sample size, to our surprise buntanetap improved cognition in AD patients and motor function in PD patients, both statistically significantly.

3. annovisbio.com annovisbio.com/press-release/annovis-announces-novel-biomarker-data-in-alzheimers-patients-supporting-buntanetaps-potential-as-a-disease-modifying-treatment

Annovis Announces Novel Biomarker Data in Alzheimer's ... Buntanetap has previously demonstrated clinical benefits in the Phase 2/3 study, where mild AD patients saw significant cognitive improvement.

4. neurologylive.com neurologylive.com/view/fda-accepts-amended-protocol-phase-3-trial-buntanetap-alzheimer-disease

FDA Accepts Amended Protocol for Phase 3 Trial of ... Phase 2/3 data revealed buntanetap improved cognitive scores in patients with Alzheimer disease, with the highest dose (30 mg) showing a 3 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06709014

NCT06709014 | A Double-blind Dual Study Assessing ... The goal of this clinical trial is to learn if buntanetap/Posiphen works to treat early Alzheimer's disease in adults aged 55-85.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10984053/

A multicenter, randomized, double-blind, placebo-controlled ... There were three primary objectives of the study: 1) to assess safety and tolerability of Posiphen in people with early AD, including people ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02925650

Safety, Tolerability, PK and PD of Posiphen® in Subjects ... This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with ...