Senicapoc in Alzheimer's Disease

NCT ID: NCT04804241

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-18
• Study Completion Date: 2026-06-30

Brief 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.

Detailed Description

The investigators will study up to 55 patients (8:3 active treatment with 10 mg/day maintenance dose: placebo) over 52 weeks in either the Sacramento or East Bay locations the University of California Davis Alzheimer's Disease Research Center (ADRC), with cognitive outcomes, blood, and CSF markers of neuroinflammation. This pilot study will provide an estimate of treatment effect size on cognitive trajectory, daily function, and brain atrophy. The trial will last 1 year (52 weeks on 10 mg/day of active drug or placebo) with primary efficacy measures at baseline, week 26, and week 52. Additional safety monitoring visits will occur at weeks 4, 12, and 36 including physical exams, measurement of blood pressure, vital signs, safety labs, electrocardiogram recordings, collection of Adverse Events and Concomitant Medications. The study will culminate with a visit at 78 weeks (26 weeks after last dose, allowing full wash-out from the central nervous system (CNS)) to test if the previously treated and untreated groups show any differences, as would be expected if Senicapoc treatment for 1 year was disease-modifying. All participants will be required to participate in either the CSF Sub-study or the Amyloid Positron Emission Tomography (PET) Sub-study. All participants will be required to participate in the Cognitive Event Related Potential (ERP) Sub-study.

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

10 mg daily Senicapoc

10 mg daily Senicapoc for 52 weeks

Group Type: EXPERIMENTAL

Senicapoc

Intervention Type: DRUG

10 mg oral tablet

Placebo Group

Placebo daily for 52 weeks

Group Type: PLACEBO_COMPARATOR

Placebo Tablet

Intervention Type: OTHER

Placebo Oral Tablet

Interventions

Senicapoc

10 mg oral tablet

Intervention Type: DRUG

Placebo Tablet

Placebo Oral Tablet

Intervention Type: OTHER

Other Intervention Names

TRAM-34

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alzheimer's Drug Discovery Foundation

OTHER

Sponsor Role: collaborator

Alzheimer's Association

OTHER

Sponsor Role: collaborator

Biossil Inc.

INDUSTRY

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Olichney, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Davis Alzheimer's Disease Center

Sacramento, California, United States

Site Status: RECRUITING

UC Davis Alzheimer's Disease Center East Bay

Walnut Creek, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rita Venua

Role: CONTACT

rmvenua@ucdavis.edu

(916) 734-1708

Selene Leal Carrillo

Role: CONTACT

slealcarrillo@ucdavis.edu

(925) 357-6914

Facility Contacts

Martha Forloines, PhD

Role: primary

mrforloines@ucdavis.edu

916-734-5223

Martha Forloines, PhD

Role: primary

mrforloines@ucdavis.edu

916-734-5223

Related Links

https://studypages.com/s/a-study-of-senicapoc-in-alzheimers-disease-763405/?ref=gallery

Learn more or sign up for the study here!

Other Identifiers

945869

Identifier Type: -

Identifier Source: org_study_id