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

NCT ID: NCT04994483

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 804 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-03
• Study Completion Date: 2024-10-02

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.

Conditions

Alzheimer Disease

Study Design

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

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Simufilam 100 mg

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

Group Type: EXPERIMENTAL

Simufilam

Intervention Type: 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.

Interventions

Simufilam

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

PTI-125

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Evidence for AD pathophysiology, confirmed either prior to or during screening.

3. MMSE score ≥ 16 and ≤ 27 at screening.

4. Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.

5. 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.

6. The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.

7. Availability of a study partner.

8. 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.

9. 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.

Exclusion Criteria

1. A neurologic condition other than AD that significantly contributes to the subject's dementia.

2. Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.

3. 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).

4. Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.

5. Alcohol or substance use disorder within 2 years of screening.

6. MRI presence of cerebral vascular or other significant pathology.

7. History of transient ischemic attack or stroke within 12 months of screening

8. Seizure within 12 months of screening.

9. Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.

10. Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.

11. Insufficiently controlled diabetes mellitus or hypertension.

12. Body mass index < 18.5 or > 37.5.

13. History or diagnosis of clinically significant cardiac disease

14. Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 87 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Premier Research Group plc

UNKNOWN

Sponsor Role: collaborator

Cassava Sciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Kupiec, MD

Role: STUDY_CHAIR

Cassava Sciences

Locations

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

Lady Lake, 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

Central Miami Medical Institute (GMI)

Miami, Florida, United States

New Horizon Research Center

Miami, Florida, United States

Luminous Clinical Research

Miami, Florida, United States

Quantam Clinical Trials

Miami Beach, Florida, United States

South Florida Research Phase I-IV INC

Miami Springs, Florida, United States

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States

Renstar Medical Research

Ocala, Florida, United States

Charter Research

Orlando, 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

Q & T Research

Sherbrooke, Quebec, Canada

Diex Research Sherbrooke Inc.

Sherbrooke, Quebec, Canada

Alpha Recherche Clinique

Québec, , Canada

Countries

United States; Australia; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PTI-125-07

Identifier Type: -

Identifier Source: org_study_id