Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease

NCT04994483 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PTI-125-07
• Study Type: interventional
• Target: 804
• Locations: 3 countries
• Sites: 88

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)

  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).

  Baseline (Study Day 1) to Week 52

• Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

  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.

  Baseline (Study Day 1) to Week 52

Secondary Outcomes (5)

• Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)

  Baseline (Study Day 1) to Week 52

• Change From Baseline in the Neuropsychiatric Inventory (NPI)

  Baseline (Study Day 1) to Week 52

• Change From Baseline in the Mini-Mental State Exam (MMSE)

  Baseline (Study Day 1) to Week 52

• Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)

  Baseline (Study Day 1) to Week 52

• Change From Baseline in the Zarit Burden Interview (ZBI)

  Baseline (Study Day 1) to Week 52

Other Outcomes (2)

• Changes From Baseline in Plasma Biomarkers

  Baseline (Study Day 1) to Week 52

• Changes From Baseline in the Plasma SavaDx Biomarker

  Baseline (Study Day 1) to Week 52

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks

Drug: Placebo

Simufilam 100 mg

EXPERIMENTAL

Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks

Drug: Simufilam

Interventions

Simufilam DRUG

Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.

Also known as: PTI-125

Simufilam 100 mg

Placebo DRUG

Matching placebo given b.i.d. for 52 weeks.

Placebo

Eligibility Criteria

• Age: 50 Years - 87 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cassava Sciences, Inc.: lead
• Premier Research: collaborator

Study Sites (88)

MDFirst Research

Chandler, Arizona, 85286, United States

Location

CCT Research - Gilbert Neurology Partners

Gilbert, Arizona, 85297, United States

Location

Xenoscience, Inc.

Phoenix, Arizona, 85004, United States

Location

Advanced Research Center, Inc

Anaheim, California, 92805, United States

Location

Axiom Research, LLC

Colton, California, 92324, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Sun Valley Research Center, Inc.

Imperial, California, 92251, United States

Location

Senior Clinical Trials

Laguna Hills, California, 92653, United States

Location

Artemis Institute for Clinical Research

Riverside, California, 92503, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Mountain Neurological Research Center

Basalt, Colorado, 81621, United States

Location

Colorado Neurological Research Center, PC

Denver, Colorado, 80210, United States

Location

CT Clinical Research

Cromwell, Connecticut, 06416, United States

Location

Topaz Clinical Research

Apopka, Florida, 32703, United States

Location

Neurology Offices of South Florida

Boca Raton, Florida, 33428, United States

Location

Boynton Beach Medical Research Institute (GMI)

Boynton Beach, Florida, 33437, United States

Location

K2 Medical Research - Clermont

Clermont, Florida, 34711, United States

Location

Arrow Clinical Trials

Daytona Beach, Florida, 32117, United States

Location

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Velocity Clinical Research, Hallandale Beach

Hallandale, Florida, 33009, United States

Location

Galiz Research

Hialeah, Florida, 33016, United States

Location

Infinity Clinical Research - Sunrise

Hollywood, Florida, 33024, United States

Location

CNS Healthcare - Jacksonville

Jacksonville, Florida, 32256, United States

Location

Charter Research

Lady Lake, Florida, 32162, United States

Location

Segal Trials - West Broward Outpatient Site

Lauderhill, Florida, 33319, United States

Location

ClinCloud

Maitland, Florida, 32751, United States

Location

Merritt Island Medical Research, LLC

Merritt Island, Florida, 32952, United States

Location

Central Miami Medical Institute (GMI)

Miami, Florida, 33125, United States

Location

New Horizon Research Center

Miami, Florida, 33165, United States

Location

Luminous Clinical Research

Miami, Florida, 33186, United States

Location

Quantam Clinical Trials

Miami Beach, Florida, 33140, United States

Location

South Florida Research Phase I-IV INC

Miami Springs, Florida, 33166, United States

Location

Suncoast Clinical Research, Inc.

New Port Richey, Florida, 34652, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Charter Research

Orlando, Florida, 32803, United States

Location

Combined Research Orlando Phase I-IV

Orlando, Florida, 32807, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Clinical Research of Brandon, LLC (Tampa)

Tampa, Florida, 33603, United States

Location

Stedman Clinical Trials

Tampa, Florida, 33613, United States

Location

Premier Research Institute at Palm Beach Neurology

West Palm Beach, Florida, 33407, United States

Location

Velocity Clinical Research, Boise

Meridian, Idaho, 83642, United States

Location

Northwestern Medicine Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

Ascension Via Christi Research

Wichita, Kansas, 67214, United States

Location

Neuro Medical Clinic of Central Louisiana, LLC

Alexandria, Louisiana, 71301, United States

Location

Boston Neuro Research Center

North Dartmouth, Massachusetts, 02747, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

CCT Research - Papillion Research Center

Papillion, Nebraska, 68046, United States

Location

Advanced Clinical Institute, Inc

West Long Branch, New Jersey, 07764, United States

Location

Albuquerque Neuroscience, Inc

Albuquerque, New Mexico, 87109, United States

Location

Dent Neurologic Institute

Amherst, New York, 14226, United States

Location

Parker Jewish Institute for Health Care & Rehabilitation

New Hyde Park, New York, 11040-1433, United States

Location

Mid Hudson Medical Research

New Windsor, New York, 12553, United States

Location

NY Neurology Associates

New York, New York, 10003, United States

Location

University of Rochester Medical Center - Alzheimer's Disease Care, Research and Education Program

Rochester, New York, 14620, United States

Location

Five Town Neuroscience Research

Woodmere, New York, 11598, United States

Location

Triad Clinical Trials, LLC

Greensboro, North Carolina, 27410, United States

Location

Alzheimer's Memory Center

Matthew, North Carolina, 28105, United States

Location

Insight Clinical Trials LLC

Beachwood, Ohio, 44122, United States

Location

NeuroScience Research Center, LLC

Canton, Ohio, 44718, United States

Location

Dayton Center for Neurological Disorders

Centerville, Ohio, 45459, United States

Location

Summit Research Network, LLC

Portland, Oregon, 97210, United States

Location

Brian Abaluck, LLC

Malvern, Pennsylvania, 19355, United States

Location

Global Medical Institutes/Scranton Medical Institute - Moosic Division

Moosic, Pennsylvania, 18507, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Palmetto Clinical Research

Summerville, South Carolina, 29485, United States

Location

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

Location

Senior Adults Specialty Research, Inc

Austin, Texas, 78757, United States

Location

Texas Neurology, PA

Dallas, Texas, 75206, United States

Location

Baylor Scott & White Research Institute

Dallas, Texas, 75231, United States

Location

Mt. Olympus Medical Research, LLC

Katy, Texas, 77450, United States

Location

Grayline Research Center

Wichita Falls, Texas, 76309, United States

Location

Green Mountain Research Institute, Inc.

Rutland, Vermont, 05701, United States

Location

Re:Cognition Health

Fairfax, Virginia, 22031, United States

Location

Memory and Brain Wellness Center at Harborview

Seattle, Washington, 98104, United States

Location

KaRa MINDS

Macquarie Park, New South Wales, 2113, Australia

Location

The University of Queensland

Herston, Queensland, 4029, Australia

Location

Impact Health Pty Ltd.

Southport, Queensland, 4215, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Delmont Private Hospital

Glen Iris, Victoria, 3146, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, 8009, Australia

Location

LMC Clinical Research - London

London, Ontario, N6A 5R9, Canada

Location

Bluewater Clinical Research Group Inc

Sarnia, Ontario, N7T 4X3, Canada

Location

Q & T Research

Sherbrooke, Quebec, J1J 2G2, Canada

Location

Diex Research Sherbrooke Inc.

Sherbrooke, Quebec, J1L0H8, Canada

Location

Alpha Recherche Clinique

Québec, G3K 2P8, Canada

Location

Related Publications (1)

• Kupiec JW, Porsteinsson AP, Turner RS, Hendrix S, Mallinckrodt C, Khan A, Cohen I, Liss J, Clarnette R, Park KH, Hernandez AM, Burns LH. Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2026 Jan 1:100469. doi: 10.1016/j.tjpad.2025.100469. Online ahead of print.

  PMID: 41500915 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Simufilam

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Cassava Sciences, Inc.

ClinicalTrials.gov@cassavasciences.com

737-910-1045

Study Officials

• James Kupiec, MD

  Cassava Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized treatments will be assigned by subject numbers in a randomly generated numeric sequence. Randomization (1:1) will be stratified by low or high Mini-Mental State Exam (MMSE; 16-20 and 21-27). The randomization code will not be revealed to study subjects, Investigators, clinical staff, study monitors, or the Sponsor until all subjects have completed therapy and the database has been finalized and locked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 750 patients will be enrolled into the study. All patients will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks.

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 6, 2021
• Study Start: November 3, 2021
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9); CA (5); US (74)