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

Plain English Summary

Senicapoc in Alzheimer's Disease is a Phase 2 clinical trial sponsored by University of California, Davis studying Mild Cognitive Impairment, Alzheimer Disease. This study tests a drug called Senicapoc to see if it can help people with early signs of Alzheimer's disease. It is for individuals aged 55-85 who have mild cognitive impairment or early Alzheimer's disease. Participants will take either Senicapoc or a placebo (a sugar pill) for 52 weeks and undergo regular assessments. There are no approved alternatives specifically for this stage of Alzheimer's, making new treatments crucial. The trial aims to enroll 55 participants.

Official Summary

Development of novel disease-modifying therapies for Alzheimer's disease (AD) remains of paramount importance. This study will be a Phase II randomized clinical trial testing Senicapoc in patients with mild or prodromal AD. This will be a small Proof of Mechanism study to prove biological activity and target engagement in humans with early AD. The investigators will study up to 55 patients over 52 weeks, with primary outcomes being Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) scores and blood and cerebrospinal fluid (CSF) markers of neuroinflammation. This pilot study will provide an estimate of treatment effect size on cognitive trajectory, daily function, and brain atrophy.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 55 and 85 years old and have been diagnosed with mild cognitive impairment or early Alzheimer's disease. You must be able to communicate in English or Spanish and have a study partner who spends at least 6 hours a week with you. You cannot join if you have unstable medical conditions, certain brain-related issues, a history of recent major depression or suicide attempts, or are unable to undergo MRI scans. This trial is studying Mild Cognitive Impairment, Alzheimer Disease, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see if Senicapoc improves cognitive function, measured by a standard test, and reduces markers of inflammation in the brain and blood. The specific primary outcome measures are: Change from Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog 13) score (Baseline, Week 26, Week 52); Change from Baseline to Week 52 in levels of Cerebrospinal fluid (CSF) biomarkers: IL-1β, IL-6, TNF-α, MCP-1, and IL-10 (Baseline, Week 52); Change from Baseline to Week 52 in levels of serum biomarkers: IL-6, TNF-α, MCP-1, and IL-10 and high sensitivity C-Reactive protein (Baseline, Week 52). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a new potential treatment to slow the progression of Alzheimer's disease, addressing a significant unmet need in managing this condition. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Mild Cognitive Impairment, Alzheimer Disease, where improved treatment options are needed.

Investor Insight

This Phase 2 trial is a small, early-stage study focused on understanding how Senicapoc works, with potential for larger trials if successful, indicating a possible future treatment option in the larg Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if Senicapoc is a suitable option for you and what the potential benefits and risks are. Participation involves taking a daily pill (either Senicapoc or a placebo) for about a year and attending regular clinic visits for tests and assessments. You will need to have a reliable study partner who can help provide information about your daily functioning. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 55 participants

Interventions

• DRUG: Senicapoc — 10 mg oral tablet
• OTHER: Placebo Tablet — Placebo Oral Tablet

Primary Outcomes

• Change from Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog 13) score (Baseline, Week 26, Week 52)
• Change from Baseline to Week 52 in levels of Cerebrospinal fluid (CSF) biomarkers: IL-1β, IL-6, TNF-α, MCP-1, and IL-10 (Baseline, Week 52)
• Change from Baseline to Week 52 in levels of serum biomarkers: IL-6, TNF-α, MCP-1, and IL-10 and high sensitivity C-Reactive protein (Baseline, Week 52)

Secondary Outcomes

• Change from Screening in the Clinical Dementia Rating (CDR) sum of boxes score (Screening, Week 26, Week 52)
• Change from Baseline in the Everyday Cognition (ECog) score (Baseline, Week 26, Week 52)
• Change from Screening in Montreal Cognitive Assessment (MoCA) score (Screening, Week 26, Week 52)
• Change from Baseline to Week 52 in Spanish English Neuropsychological Assessment Scales (SENAS) memory score (Baseline, Week 52)
• Change from Baseline to Week 52 in Spanish English Neuropsychological Assessment Scales (SENAS) executive composite score (Baseline, Week 52)

Full 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 da

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment
• Dementia
• Neurodegenerative Diseases
• Cognitive Impairment
• Geriatric Psychiatry
• Neurology
• Brain Health
• Inflammation
• Central Nervous System Disorders

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