A 6-month & 18-month Prospective, Randomized, Placebo-controlled, Double-blind Dual Clinical Trial Investigating Efficacy and Safety of Buntanetap in Treating Participants of Early Alzheimer's Disease
The goal of this clinical trial is to learn if buntanetap/Posiphen works to treat early Alzheimer's disease in adults aged 55-85. It will also learn about the safety of buntanetap/Posiphen. The main questions it aims to answer are: * Does buntanetap/Posiphen improve cognition as measured by ADAS-Cog13? * Does buntanetap/Posiphen improve function as measured by ADCS-iADL? * What medical issues do participants have, if any, when taking buntanetap/Posiphen? Researchers will compare buntanetap/Posiphen to a placebo (a look-alike substance that contains no drug) to see if buntanetap/Posiphen works to treat early Alzheimer's disease. Participants will: * Take buntanetap/Posiphen or a placebo every day for 18 months * Visit the clinic periodically for checkups, tests, and questionnaires (screening visits, enrollment, month 1, month 3, month 6, month 9, month 12, month 15, month 18), including a volumetric MRI at month 6 and month 18 * Complete pre- and post-clinic visit phone calls
• Diagnosis of AD according to the 2024 National Institute on Aging and Alzheimer's Association criteria.
• Male or female, aged 55 - 85 years.
• MMSE 20-28 at screening and baseline.
• CDR global score=0.5 or 1, with memory box score at least 0.5 at screening and baseline.
• Positive for amyloid beta as defined by plasma p-tau217 level at screening.
• Neuroimaging (MRI) consistent with the clinical diagnosis of AD and without findings of significant exclusionary abnormalities (see exclusion criteria # 4). A historical MRI, up to 1 year prior to screening, may be used as long as there have been no interval clinical neurologic events that may suggest a change in the MRI scan.
• 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 on 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 one month 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. 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 evaluated 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 participants 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,
⁃ IUD,
⁃ IUS,
⁃ Bilateral tubal occlusion.
⁃ General cognition and functional performance sufficiently preserved that the subject can provide written informed consent. At re-consent, a legally authorized representative may co-sign if participants do not meet the general cognition and functional performance needed in the opinion of the investigator.
⁃ No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
⁃ Stability of permitted medications for at least 4 weeks prior to screening. Refer to Concomitant Medications section for details on prohibited and permitted medications.
∙ Cholinesterase inhibitors and/or memantine medication,
‣ Anticonvulsant medications used for epilepsy or mood stabilization, or neuropathic pain indications, and have not had a breakthrough seizure in 3 years prior to screening
‣ Mood-stabilizing psychotropic agents including, but not limited to, lithium.
⁃ Adequate visual and hearing ability (physical ability to perform all the study assessments).
⁃ Participants previously exposed to buntanetap can still be included in the study after a 28-day wash out period.