A Multicenter, Randomized, Double-masked, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NTRX-07 in Subjects With Mild Cognitive Impairment or Mild to Moderate Alzheimer's Disease
Objective: * To assess the safety and tolerability of NTRX-07 in patients with AD. * Safety and tolerability will be measured by monitoring any side effects or adverse events in participants during and after the treatment period. Secondary Objective: * To study how NTRX-07 is processed by the body, including how it is absorbed, distributed, metabolized, and eliminated. * This includes measuring the drug levels in the blood and cerebrospinal fluid (CSF) over time. 3. Study Design • Type of Study: o A randomized, double-masked, placebo-controlled study. Randomized means participants are randomly assigned to receive either the actual drug (NTRX-07) or a placebo (an inactive substance). Double-masked indicates that neither the participants nor the researchers know who receives the real drug or the placebo, reducing bias and ensuring objective results. • Participants: * 48 individuals with MCI or mild to moderate AD. • Treatment Groups: * Participants will be split into two groups: 24 will receive NTRX-07, and 24 will receive a placebo. • Duration: * The study will last up to 7-10 weeks for each participant, including a 28-day period during which they take the drug or placebo daily. 4. Study Procedures • Screening Period: * Before starting the treatment, participants will undergo a screening period of up to 45 days. During this time, they will have tests to confirm their eligibility, including physical exams, blood tests, cognitive assessments, and brain imaging (MRI). • Treatment Period (28 days): * Participants will take the study drug or placebo daily for 28 days. During this period, they will visit the study center for evaluations, including safety checks, cognitive tests, blood and CSF sampling, and EEG tests (to measure brain activity). • Follow-Up: * After the treatment period, participants will have a follow-up visit 7 days later for final safety assessments. 5. Safety Monitoring and Assessments * The study's primary focus is on safety. Researchers will monitor participants closely for any adverse events, such as side effects, throughout the study. * Safety assessments will include monitoring vital signs (blood pressure, heart rate, temperature), conducting laboratory tests (blood and urine analysis), performing physical examinations, and using electrocardiograms (ECGs) to monitor heart health. 6. Exploratory Assessments • Although this study primarily focuses on safety, researchers will also conduct exploratory assessments to observe any potential positive effects of NTRX-07 on brain function and symptoms of AD. These will include: o Cognitive Testing: * Standard tests like the AD Assessment Scale-Cognitive Subscale (ADAS-cog) and the Mini-Mental State Examination (MMSE) will be used to evaluate any changes in cognitive function. o Brain Imaging: * MRI scans will help assess changes in brain structure and inflammation. o Biomarkers: * Blood and CSF samples will be analyzed for specific biomarkers related to inflammation, brain health, and AD progression. 7. Eligibility Criteria * Inclusion Criteria: * Individuals aged 65-88 with a confirmed diagnosis of MCI or mild to moderate AD. * Must have a caregiver who can assist with the study requirements. * Must be able to undergo specific procedures like MRI scans and CSF sampling. * Exclusion Criteria: * Individuals with other significant health conditions or history of neurological disorders other than AD. * Those currently participating in another clinical trial or have certain medication restrictions. 8. Importance of the Study AD is a progressive condition that affects memory, thinking, and behavior. Current treatments only manage symptoms temporarily, and there is an need for new therapies. NTRX-07 is a novel drug that has shown promise in animal studies, potentially reducing brain inflammation, clearing harmful proteins, and improving memory and learning. This study is an essential step toward understanding if NTRX-07 can offer a safe and effective treatment option for people with AD. 9. Summary This clinical trial is designed to test the safety and processing of a new drug, NTRX-07, in people with MCI or mild to moderate AD. Participants will be carefully monitored for any side effects while researchers also gather data on the drug's impact on brain function. If successful, this study could lead to more advanced trials and, ultimately, a new treatment option for those affected by AD.
⁃ Participants must be 65-80 years of age inclusive, at the time of signing the informed consent.
⁃ Clinical Dementia Rating (CDR) of 0.5 - 2.0; and education-adjusted Logical Memory II scores consistent with MCI or mild to moderate AD (\<1.5 SD below mean cutoff). MMSE 12-26
⁃ pTau 217 consistent with AD, or recent amyloid test panel within 2 years. The test must be after any previous participation in an anti-amyloid MAB trial.
⁃ Participants who have been in a previous amyloid-directed MAB study must have a negative ARIA report after the study.
⁃ Confirmed medical documentation of AD symptoms onset at age 60 or later.
⁃ No active depression and a Geriatric Depression Score of \< 6.
⁃ No change in acetylcholinesterase inhibitors or memantine for the previous six months and is not expected to start an acetylcholinesterase inhibitor during the duration of the study.
⁃ Living at home, with a reliable caregiver who sees them at least 3 times/week for 10 hours or more and can oversee the administration of the study drug.
⁃ Provide written informed consent and willingness as documented by a signed informed consent form; responsible caregiver must also provide written consent.
‣ Body weight within 55-110 kg and body mass index (BMI) within the range 18-35 kg/m2 (inclusive)
‣ Male or Female • Male participants: Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days, after the last dose of study intervention:
∙ Refrain from donating sperm PLUS, either:
∙ Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent ba sis) and agree to remain abstinent.
∙ OR
• Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
• Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.
‣ Female participants: Must be a woman of nonchildbearing potential (WONCBP) (at least two years post-menopause or surgically sterile).