Senicapoc in Alzheimer's Disease

NCT04804241 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 945869
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

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.

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Keywords

Amnestic Mild Cognitive Impairment (MCI); Mild AD dementia; Senicapoc

Outcome Measures

Primary Outcomes (3)

• Change from Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog 13) score

  ADAS-Cog 13 is a scale used to measure cognitive dysfunction in a number of neural domains. Total scores range from 0-70, with higher scores indicating greater cognitive impairment and a worse outcome.

  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

  A lumbar puncture will be done and CSF collected at baseline prior to initiating study treatment and at Week 52 at the end of study treatment

  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

  Blood draws will be done and serum processed at baseline prior to initiating study treatment and at Week 52 at the end of study treatment

  Baseline, Week 52

Secondary Outcomes (16)

• 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

Study Arms (2)

10 mg daily Senicapoc

EXPERIMENTAL

10 mg daily Senicapoc for 52 weeks

Drug: Senicapoc

Placebo Group

PLACEBO COMPARATOR

Placebo daily for 52 weeks

Other: Placebo Tablet

Interventions

Senicapoc DRUG

10 mg oral tablet

Also known as: TRAM-34

10 mg daily Senicapoc

Placebo Tablet OTHER

Placebo Oral Tablet

Placebo Group

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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,

Sponsors & Collaborators

• University of California, Davis: lead
• Biossil Inc.: collaborator
• Alzheimer's Drug Discovery Foundation: collaborator
• Alzheimer's Association: collaborator

Study Sites (2)

University of California, Davis Alzheimer's Disease Center

Sacramento, California, 95817, United States

RECRUITING

UC Davis Alzheimer's Disease Center East Bay

Walnut Creek, California, 94598, United States

RECRUITING

Related Links

• Learn more or sign up for the study here!

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

senicapoc; TRAM 34

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• John Olichney, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rita Venua

CONTACT

(916) 734-1708; rmvenua@ucdavis.edu

Selene Leal Carrillo

CONTACT

(925) 357-6914; slealcarrillo@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. All subjects and staff will be blinded to treatment allocation. Investigational drug pharmacy will maintain unblinded randomization information.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 3 to 1 to receive active study medication versus placebo.

Study Record Dates

• First Submitted: March 7, 2021
• First Posted: March 18, 2021
• Study Start: March 18, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 29, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: Proposals may be submitted to Principal Investigator up to 36 months following article publication. Information regarding submitting proposals and accessing data can be found on the UC Davis Alzheimer's Disease Research Center webpage.

Locations

US (2)