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)
Overview
- Phase
- Phase 2
- Intervention
- PrimeC
- Conditions
- Alzheimer Disease
- Sponsor
- NeuroSense Therapeutics Ltd.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- To assess safety and tolerability of PrimeC in mild to moderate AD patients (change from baseline to 12 months)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
20 subjects with mild to moderate AD will be enrolled in the study and randomized at a 1:1 ratio to receive the study drug or placebo tablets, respectively. All subjects will be administered the drug/placebo twice daily (BID), two tablets each time, for 52 weeks.
Subjects will be allowed to receive standard of care (SOC) treatment of approved products or their combination. Subjects will be evaluated every 3 months for safety and tolerability.
Detailed Description
This is a Phase II, Randomized, Single-center, Prospective, Double-Blind, Placebo-Controlled Study, to evaluate Safety, Tolerability, target engagement and efficacy of PrimeC in subjects with mild to moderate AD. Subjects who meet the inclusion criteria and none of the exclusion criteria and who provide a signed Informed Consent will be enrolled in the study. 20 subjects with mild to moderate AD will be enrolled in the study and randomized at a 1:1 ratio to receive the study drug or placebo tablets, respectively. All subjects will be administered the drug/placebo twice daily (BID), two tablets each time, for 52 weeks. Subjects will be allowed to receive standard of care (SOC) treatment of approved products or their combination (rivastigmine, donepezil, galantamine, memantine, donezepil, aducanumab, and lecanemab). Subjects will be evaluated every 3 months for safety and tolerability (adverse events, safety laboratory, vital signs, ECG, withdrawal rates and reasons). Subjects will be evaluated for efficacy at baseline and after 12 months for CSF biomarkers and clinical outcomes (CDR, ADAS COG 14, ADCS-iADL, MMSE), for blood biomarkers at baseline, 6 and 12 months, and for C-SSRS every 3 months. A remote follow up (via phone call) will be conducted 1 month after baseline visit in order to confirm investigational drug compliance according to the protocol and potential AEs. Adverse events (AEs) including any death, will be recorded throughout the study. During the study, the sponsor, the PI, the outcome assessor, the subjects and all staff involved in the collection and recording of the clinical and laboratory data will be blinded to the treatment assignment. In addition, all aspects of data management and clean-up will be done using blinded datasets. Following completion of 12 months of treatment, data lock will be performed, and data will be analyzed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Males or females between the ages of 55 and 85 years of age, inclusive
- •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
- •AD patients with a score of 18 to 24 on MMSE at screening.
- •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.
- •18 \< BMI \< 30
- •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.
- •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.
- •CT or MRI available within 3 months before the lumbar puncture.
- •Presence of pTau 181 in CSF at screening
Exclusion Criteria
- •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.
- •Stroke or Transient Ischemic Attack (TIA) within 6 months of screening visit.
- •History of severe head trauma with documented loss of consciousness or with radiological findings associated with the injury, leading to other neurological deficits.
- •Any contraindication to conduct lumber puncture.
- •Major depressive disorder according to DSM-V criteria requiring hospitalization within the previous 90 days before screening.
- •Suicidal ideation and behavior assessed by C-SSRS.
- •Serum B12 clinically significantly below the lower limit of normal at screening
- •Patients with history or current evidence of clinical significant peripheral neuropathy. The severity of the peripheral neuropathy will be determined by the investigator.
- •Patients who take tizanidine
- •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.
Arms & Interventions
PrimeC
2 tablets of PrimeC administered twice daily (4 tablets a day), total daily dose of 1360 mg ciprofloxacin and 136 mg celecoxib orally.
Intervention: PrimeC
Placebo
2 tablets of Placebo administered twice daily (4 tablets a day). Placebo tablets are matched in size, color and taste.
Intervention: Placebo
Outcomes
Primary Outcomes
To assess safety and tolerability of PrimeC in mild to moderate AD patients (change from baseline to 12 months)
Time Frame: 12 months
* Incidence and severity of treatment-emergent adverse events (TEAEs) * Number (%) of subjects who discontinued treatment prematurely * Number (%) of subjects who discontinued treatment prematurely due to AEs * Number (%) of subjects with clinically significant abnormal laboratory values following treatment
Secondary Outcomes
- To assess the effect of PrimeC on cognitive functioning and activities of daily living in mild to moderate AD patients (change from baseline to 12 months)(12 months)