Testing Senicapoc for Mild Cognitive Impairment and Alzheimer's Disease

Proof of Mechanism Study of Senicapoc in Mild or Prodromal Alzheimer's Disease

This study is testing if a new drug called Senicapoc can help people with mild cognitive impairment or early Alzheimer's disease improve their thinking and daily activities over a year.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 55 Years to 85 Years
• Sex: All
• Sponsor: University of California, Davis (Academic / other)
• Drugs / interventions: radiation
• Locations: 2 sites (Sacramento, California and 1 other locations)
• Trial ID: NCT04804241 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial aims to evaluate the efficacy of Senicapoc in patients with mild or prodromal Alzheimer's disease. The study will enroll up to 55 participants who will be randomized to receive either Senicapoc or a placebo for 52 weeks. Primary outcomes will include cognitive assessments and biomarkers of neuroinflammation measured through blood and cerebrospinal fluid. The trial will also assess the treatment's impact on cognitive trajectory, daily functioning, and brain atrophy over the study period.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 55-85 with a diagnosis of mild cognitive impairment or mild Alzheimer's disease.

Not a fit: Patients with severe cognitive impairment or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel disease-modifying therapy for patients with early Alzheimer's disease.

How similar studies have performed: While this approach is novel, other studies targeting neuroinflammation in Alzheimer's have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Age 55-85
* Fluent in either English or Spanish
* Willing to be randomized to active drug (10 mg Senicapoc) vs. placebo (3:1 ratio)
* Clinical Dementia Rating (CDR) global score of 1 or 0.5
* Education adjusted scores between 12-28 on the Montreal Cognitive Assessment (MoCA) at the Screening visit.
* A consensus clinical diagnosis of either amnestic Mild Cognitive Impairment (MCI) or mild AD dementia. Diagnoses are made by a comprehensive case conference review for all participants in the ADRC longitudinal cohort and all CADC referrals, resulting in a consensus diagnosis made according to current research criteria. For patients referred from other clinics, the case will be reviewed by a study physician and neuropsychologist and only patients who satisfy criteria for probable AD (McKhann et al 1984) or amnestic MCI (Petersen et al 2004) will be eligible for enrollment.
* Vision (with or without correction) of at least 20/50 for distant vision
* All participants will need a study partner informant who has at least 6 hours of contact per week with the participant. The study partners are used to help answer questions on the subject's behalf, since many of them will be impaired and may need assistance with providing accurate information. The study partners are not asked to provide any opinions or judgements about the subjects.
* For Females of childbearing potential: Must agree to practice a highly effective method of contraception throughout the study until completion of the Week 78 follow up visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of less than 1% per year when used correctly and consistently.

Exclusion Criteria:

* Unstable medical illnesses including hepatic insufficiency (elevated ALT, AST, or GGT; or low albumin attributable to liver disease), renal insufficiency (CK-EPI stage 4 or higher, or estimated GFR \<30)
* Unstable ischemic cardiovascular disease, respiratory failure, moderate or severe congestive heart failure - New York Heart Association class III or IV, cancer, unstable hematologic disease or a life expectancy of \<3 years
* Use of experimental AD treatments
* Unable to undergo MRI scanning (e.g. pacemaker, metallic implants, severe claustrophobia)
* History of chronic psychiatric illness (e.g. schizophrenia), any episode of major depression within last 2 years, or current Geriatric Depression Scale (GDS) \> 6, any recent suicide attempts or suicidal ideation. Subjects with a diagnosis of bipolar disorder may be included if they have been clinically stable for a minimum of 3 years prior to the Screening visit. Clinical stability to be determined by the Principal Investigator.
* History of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), head trauma resulting in any persistent cognitive deficit
* History of alcohol or drug abuse/dependence within the past 5 years
* Known allergy to chemically related compounds (e.g. clotrimazole)
* Lack of good venous access, such that multiple blood draws would be precluded
* Regular use of any of these CNS active medications: benzodiazepines, antipsychotics, narcotics, or anti-epileptic drugs. Exceptions may be allowed by the Principal Investigator for regular use of low doses of CNS active medications. Subjects using any of these treatments will be instructed to hold their dose on the evening prior and the day of the efficacy visits (Baseline, Week 26 and Week 52). Stable doses (\> 6 weeks) of cholinesterase inhibitors or memantine will be allowed, as will stable doses of anti-depressants.
* Female subjects who are pregnant or breastfeeding or who plan to become pregnant during participation in this trial
* Inability to swallow oral tablets

Exclusions for Cerebrospinal Fluid (CSF) Sub-study:

* Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
* History of bleeding diathesis or coagulopathy,
* On anticoagulant therapy (within 14 days of lumbar puncture (LP), including but not limited to warfarin, heparin, dabigatran, rivaroxaban, and apixaban,
* Requires daily antiplatelet therapy, including but not limited to aspirin (unless \< 81mg/day), clopidogrel, dipyridamole, and ticlopiidinegrel. However, the investigators will not exclude those who can safely hold antiplatelet therapy for 7 days prior to LP. Safety will be determined by the participant's Primary Care Provider and study PI.
* For those who take antiplatelet therapy intermittently (e.g. aspirin as needed for pain), the investigators will exclude any doses within 48 hours of the LP or more than two dosses within 7 days of LP.
* platelet count less than the lower limit of normal (platelet counts between 100,000 and 150,000 mm3 are permissible as long as the investigator confirms there is no evidence of current bleeding diathesis or coagulopathy)
* The investigators will require INR/PT and aPTT labs to be done within 14 days of LP and will exclude those with INR \> 1.30 or abnormally elevated aPTT.

Exclusions for PET Sub-Study:

* Does not have good venous access, such that multiple blood draws would be precluded
* Prior radiation exposure of \> 2 rem total within last 12 months.
* Probable AD dementia patients with a global cortical SUVr \< 1.08.

Where this trial is running

Sacramento, California and 1 other locations

• University of California, Davis Alzheimer's Disease Center — Sacramento, California, United States (Recruiting)
• UC Davis Alzheimer's Disease Center East Bay — Walnut Creek, California, United States (Recruiting)

Study contacts

• Principal investigator: John Olichney, MD — University of California, Davis
• Study coordinator: Rita Venua

Conditions Mild Cognitive Impairment; Alzheimer Disease; Amnestic Mild Cognitive Impairment; Mild AD dementia; Senicapoc