Simufilam 100 Mg for Mild-to-Moderate Alzheimer's Disease
- Registration Number
- NCT04994483
- Lead Sponsor
- Cassava Sciences, Inc.
- Brief Summary
A 52-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 52 weeks. Approximately 750 participants will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated.
- Detailed Description
The primary objective of this study is to investigate the safety and efficacy of simufilam (PTI-125) in enhancing cognition and slowing cognitive and functional decline following 52-week, repeat-dose oral administration in participants with mild-to-moderate AD. Secondary objectives include the assessment of simufilam's effect on neuropsychiatric symptoms and caregiver burden. A third objective is to investigate the effect of simufilam treatment on plasma biomarkers. A limited number of research sites will be invited to participate in the pharmacokinetic (PK) and plasma biomarker sub-study. Collection of PK samples will enable an exposure-response analysis. Approximately 100 subjects will participate (50 per group). Plasma samples will be collected during the Screening Visit and again at Weeks 28 and 52. Change from Baseline for plasma biomarkers represent additional secondary endpoints.
Safety will be evaluated by adverse event monitoring, vital signs, clinical labs, and the Columbia Suicide Severity Rating Scale at every visit. Subjects will undergo magnetic resonance imaging (MRI) during screening to ensure entry criteria are met (unless recent MRI confirms entry criteria). Resting electrocardiograms will be conducted at Baseline (Study Day 1) and Weeks 4, 28, and 52. A complete physical and neurological examination will be performed at screening, and brief examinations will be performed at all other visits. Weight will be measured during the Screening Period, at Baseline (Study Day 1), and at all other visits.
An independent Data Safety Monitoring Board (DSMB) will meet periodically to review subject safety assessments and determine if dosing may continue. A charter will be developed with specific guidance for the DSMB.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 804
- Meets National Institute on Aging and Alzheimer's Association Research Framework criteria for individuals in clinical Stage 4 or 5 of the Alzheimer's continuum.
- Evidence for AD pathophysiology, confirmed either prior to or during screening.
- MMSE score ≥ 16 and ≤ 27 at screening.
- Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.
- If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization. Chronic medications for conditions other than AD (such as depression) must be prescribed at a stable dose for at least 4 weeks prior to screening.
- The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.
- Availability of a study partner.
- Individuals who have participated in a clinical study with an investigational drug targeting the underlying AD process may be permitted to participate in this study.
- Completed a COVID-19 vaccine primary series ("fully vaccinated") at least 2 weeks prior to randomization or had an unambiguous COVID-19 infection diagnosed more than 3 months before the start of the Screening Period.
Key
- A neurologic condition other than AD that significantly contributes to the subject's dementia.
- Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.
- Geriatric Depression Scale (15-item) score > 8. (Note - a subject with a score > 8 may continue in screening if, in the judgment of the Investigator, the elevated score is not attributed to a major depressive episode).
- Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.
- Alcohol or substance use disorder within 2 years of screening.
- MRI presence of cerebral vascular or other significant pathology.
- History of transient ischemic attack or stroke within 12 months of screening
- Seizure within 12 months of screening.
- Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
- Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
- Insufficiently controlled diabetes mellitus or hypertension.
- Body mass index < 18.5 or > 37.5.
- History or diagnosis of clinically significant cardiac disease
- Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks Simufilam 100 mg Simufilam Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks
- Primary Outcome Measures
Name Time Method Change from baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).
Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.
- Secondary Outcome Measures
Name Time Method Change from baseline in the integrated Alzheimer's Disease Rating Scale (iADRS) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.
Change from baseline in the Neuropsychiatric Inventory (NPI) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the NPI, a 12-item study partner interview, which records the frequency and severity of common neuropsychiatric symptoms in dementia, as well as the level of study partner distress due to each of the neuropsychiatric problems. Scores range from 0 to 144, with higher scores indicating more frequent and severe symptoms, and greater levels of partner distress.
Change from baseline in the Mini-Mental State Exam (MMSE) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the MMSE, a set of standardized questions covering several target areas: orientation, registration, attention and calculation, short-term verbal recall, naming, repetition, 3-step command, reading, writing, and visuospatial cognitive assessment. Lower scores indicate more severe impairment.
Change from baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the CDR-SB, which characterizes 6 domains of cognitive and functional performance applicable to AD and related dementias: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Higher scores indicate more severe impairment.
Change from baseline in the Zarit Burden Interview (ZBI) Baseline (Study Day 1) to Week 52 The change from baseline to Week 52 in the ZBI, a 22-item study partner questionnaire designed to assess the stress or burden experienced by caregivers of people with dementia, with a higher score indicating greater stress or burden.
Changes from baseline in plasma phospho-tau181 (P-tau181) and/or phospho-tau217 (P-tau217), and neurofilament light chain. Baseline (Study Day 1) to Week 52 Change from baseline in plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation.
Changes from baseline in the plasma SavaDx biomarker Baseline (Study Day 1) to Week 52 Change from baseline in SavaDx, a novel plasma biomarker
Trial Locations
- Locations (87)
MDFirst Research
🇺🇸Chandler, Arizona, United States
CCT Research - Gilbert Neurology Partners
🇺🇸Gilbert, Arizona, United States
Xenoscience, Inc.
🇺🇸Phoenix, Arizona, United States
Advanced Research Center, Inc
🇺🇸Anaheim, California, United States
Axiom Research, LLC
🇺🇸Colton, California, United States
ATP Clinical Research, Inc.
🇺🇸Costa Mesa, California, United States
Sun Valley Research Center, Inc.
🇺🇸Imperial, California, United States
Senior Clinical Trials
🇺🇸Laguna Hills, California, United States
Artemis Institute for Clinical Research
🇺🇸Riverside, California, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Mountain Neurological Research Center
🇺🇸Basalt, Colorado, United States
Colorado Neurological Research Center, PC
🇺🇸Denver, Colorado, United States
CT Clinical Research
🇺🇸Cromwell, Connecticut, United States
Topaz Clinical Research
🇺🇸Apopka, Florida, United States
Neurology Offices of South Florida
🇺🇸Boca Raton, Florida, United States
Boynton Beach Medical Research Institute (GMI)
🇺🇸Boynton Beach, Florida, United States
K2 Medical Research - Clermont
🇺🇸Clermont, Florida, United States
Arrow Clinical Trials
🇺🇸Daytona Beach, Florida, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Velocity Clinical Research, Hallandale Beach
🇺🇸Hallandale, Florida, United States
Galiz Research
🇺🇸Hialeah, Florida, United States
Infinity Clinical Research - Sunrise
🇺🇸Hollywood, Florida, United States
CNS Healthcare - Jacksonville
🇺🇸Jacksonville, Florida, United States
Charter Research
🇺🇸Orlando, Florida, United States
Segal Trials - West Broward Outpatient Site
🇺🇸Lauderhill, Florida, United States
ClinCloud
🇺🇸Maitland, Florida, United States
Merritt Island Medical Research, LLC
🇺🇸Merritt Island, Florida, United States
Quantam Clinical Trials
🇺🇸Miami Beach, Florida, United States
South Florida Research Phase I-IV INC
🇺🇸Miami Springs, Florida, United States
Central Miami Medical Institute (GMI)
🇺🇸Miami, Florida, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
Luminous Clinical Research
🇺🇸Miami, Florida, United States
Suncoast Clinical Research, Inc.
🇺🇸New Port Richey, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Combined Research Orlando Phase I-IV
🇺🇸Orlando, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Clinical Research of Brandon, LLC (Tampa)
🇺🇸Tampa, Florida, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
Premier Research Institute at Palm Beach Neurology
🇺🇸West Palm Beach, Florida, United States
Velocity Clinical Research, Boise
🇺🇸Meridian, Idaho, United States
Northwestern Medicine Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
Ascension Via Christi Research
🇺🇸Wichita, Kansas, United States
Neuro Medical Clinic of Central Louisiana, LLC
🇺🇸Alexandria, Louisiana, United States
Boston Neuro Research Center
🇺🇸North Dartmouth, Massachusetts, United States
Clinical Research Professionals
🇺🇸Chesterfield, Missouri, United States
CCT Research - Papillion Research Center
🇺🇸Papillion, Nebraska, United States
Advanced Clinical Institute, Inc
🇺🇸West Long Branch, New Jersey, United States
Albuquerque Neuroscience, Inc
🇺🇸Albuquerque, New Mexico, United States
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
Parker Jewish Institute for Health Care & Rehabilitation
🇺🇸New Hyde Park, New York, United States
Mid Hudson Medical Research
🇺🇸New Windsor, New York, United States
NY Neurology Associates
🇺🇸New York, New York, United States
University of Rochester Medical Center - Alzheimer's Disease Care, Research and Education Program
🇺🇸Rochester, New York, United States
Five Town Neuroscience Research
🇺🇸Woodmere, New York, United States
Triad Clinical Trials, LLC
🇺🇸Greensboro, North Carolina, United States
Alzheimer's Memory Center
🇺🇸Matthew, North Carolina, United States
Insight Clinical Trials LLC
🇺🇸Beachwood, Ohio, United States
NeuroScience Research Center, LLC
🇺🇸Canton, Ohio, United States
Dayton Center for Neurological Disorders
🇺🇸Centerville, Ohio, United States
Summit Research Network, LLC
🇺🇸Portland, Oregon, United States
Brian Abaluck, LLC
🇺🇸Malvern, Pennsylvania, United States
Global Medical Institutes/Scranton Medical Institute - Moosic Division
🇺🇸Moosic, Pennsylvania, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Palmetto Clinical Research
🇺🇸Summerville, South Carolina, United States
FutureSearch Trials of Neurology
🇺🇸Austin, Texas, United States
Senior Adults Specialty Research, Inc
🇺🇸Austin, Texas, United States
Texas Neurology, PA
🇺🇸Dallas, Texas, United States
Baylor Scott & White Research Institute
🇺🇸Dallas, Texas, United States
Mt. Olympus Medical Research, LLC
🇺🇸Katy, Texas, United States
Grayline Research Center
🇺🇸Wichita Falls, Texas, United States
Green Mountain Research Institute, Inc.
🇺🇸Rutland, Vermont, United States
Re:Cognition Health
🇺🇸Fairfax, Virginia, United States
Memory and Brain Wellness Center at Harborview
🇺🇸Seattle, Washington, United States
KaRa MINDS
🇦🇺Macquarie Park, New South Wales, Australia
The University of Queensland
🇦🇺Herston, Queensland, Australia
Impact Health Pty Ltd.
🇦🇺Southport, Queensland, Australia
Eastern Health
🇦🇺Box Hill, Victoria, Australia
Delmont Private Hospital
🇦🇺Glen Iris, Victoria, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Australian Alzheimer's Research Foundation
🇦🇺Nedlands, Western Australia, Australia
LMC Clinical Research - London
🇨🇦London, Ontario, Canada
Bluewater Clinical Research Group Inc
🇨🇦Sarnia, Ontario, Canada
Alpha Recherche Clinique
🇨🇦Québec, Quebec, Canada
Q & T Research
🇨🇦Sherbrooke, Quebec, Canada
Diex Research Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada