Evaluating PrimeC for Mild to Moderate Alzheimer's Disease

A Phase 2, Randomized, Prospective Double-Blind, Single-Center, Placebo-controlled Study to Evaluate Safety, Tolerability, Target Engagement, and Efficacy of PrimeC in Patients With Mild to Moderate Alzheimer's Disease (AD)

This study is testing a new drug called PrimeC to see if it can help people with mild to moderate Alzheimer's Disease feel better over a year while they continue their usual treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 55 Years to 85 Years
• Sex: All
• Sponsor: NeuroSense Therapeutics Ltd. (industry)
• Drugs / interventions: aducanumab, lecanemab
• Locations: 1 site (Haifa)
• Trial ID: NCT06185543 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial aims to assess the safety, tolerability, target engagement, and efficacy of PrimeC in patients diagnosed with mild to moderate Alzheimer's Disease. A total of 20 participants will be randomly assigned to receive either the study drug or a placebo, administered twice daily for 52 weeks. Participants will continue their standard of care treatments and will be monitored every three months for safety and efficacy outcomes, including various clinical and biomarker assessments. The study is designed to provide insights into the potential benefits of PrimeC in managing Alzheimer's symptoms.

Who should consider this trial

Good fit: Ideal candidates are males and females aged 55 to 85 with a diagnosis of probable Alzheimer's Disease and a Mini-Mental State Examination (MMSE) score between 18 and 24.

Not a fit: Patients with severe Alzheimer's Disease or those not meeting the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new therapeutic option for patients with mild to moderate Alzheimer's Disease.

How similar studies have performed: While similar studies have explored treatments for Alzheimer's Disease, the specific approach of using PrimeC is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Able to comprehend and willing to sign an informed consent form (ICF) and their ability to consent was estimated by an independent Neurologist or Geriatrist.
2. Males or females between the ages of 55 and 85 years of age, inclusive
3. Diagnosis of probable AD with evidence of the AD pathophysiological process according to the diagnostic criteria of the National Institute on Aging and Alzheimer's Association
4. AD patients with a score of 18 to 24 on MMSE at screening.
5. Subjects may be treated in parallel with rivastigmine, donepezil, galantamine, memantine, donezepil, aducanumab, and lecanemab or their combination. For rivastigmine, donepezil, galantamine, memantine, donezepil - 30 days of stable use prior to enrollment is required. For aducanumab and lecanemab - 3 months of stable use prior to enrollment is required.
6. 18 \< BMI \< 30
7. Patients who have a caregiver - the caregiver shall be in contact with the patient at least 10 hours per week, and can attend all visits with the patient, report on the subject's status and verify compliance with all study requirements.
8. CT or MRI available within 12 months before the enrolment to the study devoid of any structural finding which could explain the cognitive impairment, except for brain atrophy or white matter hyperintensities which can be observed in AD patients.
9. CT or MRI available within 3 months before the lumbar puncture.
10. Presence of pTau 181 in CSF at screening
11. Female with no childbearing potential (at least 1 year postmenopausal or surgical contraception)

Exclusion Criteria:

1. Any significant neurologic or medical disorders other than AD, which might be the cause of the existing cognitive deficit, such as: other neurodegenerative disease, Hydrocephalus including NPH, seizures, Huntington's disease, Amyotrophic lateral sclerosis, multiple sclerosis, systemic lupus erythematosus, progressive supranuclear palsy, neurosyphilis, HIV, learning disability, intellectual disability, hypoxic cerebral damage, relevant neoplasm, toxic exposure, or any significant medical conditions that, in the opinion of the PI would endanger the health and wellbeing of the participant.
2. Stroke or Transient Ischemic Attack (TIA) within 6 months of screening visit.
3. History of severe head trauma with documented loss of consciousness or with radiological findings associated with the injury, leading to other neurological deficits.
4. Any contraindication to conduct lumber puncture.
5. Major depressive disorder according to DSM-V criteria requiring hospitalization within the previous 90 days before screening.
6. Suicidal ideation and behavior assessed by C-SSRS.
7. Serum B12 clinically significantly below the lower limit of normal at screening
8. Patients with history or current evidence of clinical significant peripheral neuropathy. The severity of the peripheral neuropathy will be determined by the investigator.
9. Patients who take tizanidine
10. Patients with history or current clinically significant of psychiatric disorders (e.g., anxiety, depression, delirium) occurring within the last two years, which required the subject to be hospitalized.
11. Patients with known history of myasthenia gravis or myasthenic syndrome
12. No psychotropics can be started during the trial except for short acting hypnotics for sleep and or low potency neuroleptics for agitation.
13. If the patient is taking antipsychotic, antidepressant, antianxiety or any other psychotropic before enrollment to the study there was no dose change 30 days before enrollment.
14. A past history of adverse reaction/hypersensitivity to either NSAIDs, celecoxib or fluoroquinolones, ciprofloxacin and / or to the non-active components of PrimeC: Microcrystalline cellulose Avicel, Povidone K-30, Sodium lauryl sulphate, Hydroxy propyl methyl cellulose, Microcrystalline cellulose, Colloidal Silicon Dioxide, Magnesium Stearate, and Opadry Blue.
15. Any known clinically significant abnormal gastric mucosal erosion, ulcer or tumor or/and GI disorder and/or bariatric surgery
16. Known history of clinically significant impairment of renal function (eGFR \< 60)
17. Known or suspected symptomatic congestive heart and/or coronary heart disease, previous history of myocardial infarction, CABG, uncontrolled arterial hypertension, or rhythm abnormalities requiring permanent treatment
18. Known history of QT/QTc prolongation, Torsade de pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT syndrome) and the use of concomitant medications that prolong the QT/QTc interval.
19. Patients with known aortic aneurysms and heart valve regurgitation/incompetence.
20. Known or suspected diagnosis or family history of epilepsy in first degree relatives.
21. Known predisposition to tendinitis.
22. Known Impaired hepatic function.
23. Known or suspected to be a poor CYP2C9 metabolizer who also uses pharmacologic agents (prescription or over-the-counter) or herbal products known or suspected to induce or inhibit CYP2C9 within 30 days before enrollment.
24. Presence at screening of any medically significant cardiac, pulmonary, musculoskeletal, or psychiatric illness that might interfere with the subject's ability to comply with study procedures or that might confound the interpretation of clinical safety data, including, but not limited to:

    1. Mean systolic blood pressure \>160 mm Hg and/or mean diastolic blood pressure \>100 mm Hg (measurements taken after a few minutes rest) that persist on 3 successive measurements taken at least 2 minutes apart
    2. NYHA Class II or greater congestive heart failure
    3. Chronic obstructive pulmonary disease or asthma requiring daily use of bronchodilator medications
    4. Uncontrolled diabetes mellitus
25. Subject who is treated with chronic aspirin or NSAIDs and is at risk if stopped. Clopidogrel is allowed and can replace Aspirin.
26. Any contraindication for ciprofloxacin and celecoxib according to the current prescribing information.
27. Any impairment or social circumstance that, in the opinion of the Investigator, would render the subject not suitable to participate in the study.
28. Subject, or subject's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
29. Subject is participating in (or plans to participate in) any other investigational drug trial or plans to be exposed to any other investigational agent, device and/or procedure, from 30 days prior to Screening through study completion.

Where this trial is running

Haifa

• Rambam Health Care Campus — Haifa, Israel (RECRUITING)

Study contacts

• Study coordinator: Ferenc Tracik

Conditions: Alzheimer Disease