Clinical trial NCT04994483: Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Study Evaluating the Safety and Efficacy of Simufilam 100 mg Tablets in Subjects With Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Lead sponsor: Cassava Sciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Premier Research Group plc
First posted: 2021-08-06
Enrollment: 804
Sex: ALL
Minimum age (years): 50
Maximum age (years): 87
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
timeFrame: Baseline (Study Day 1) to Week 52
measure: Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline (Study Day 1) to Week 52
Secondary outcomes:
measure: Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)
timeFrame: Baseline (Study Day 1) to Week 52
measure: Change From Baseline in the Neuropsychiatric Inventory (NPI)
timeFrame: Baseline (Study Day 1) to Week 52
measure: Change From Baseline in the Mini-Mental State Exam (MMSE)
timeFrame: Baseline (Study Day 1) to Week 52
measure: Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
timeFrame: Baseline (Study Day 1) to Week 52
measure: Change From Baseline in the Zarit Burden Interview (ZBI)
timeFrame: Baseline (Study Day 1) to Week 52
Other outcomes:
measure: Changes From Baseline in Plasma Biomarkers
timeFrame: Baseline (Study Day 1) to Week 52
measure: Changes From Baseline in the Plasma SavaDx Biomarker
timeFrame: Baseline (Study Day 1) to Week 52
Locations:
city: Chandler
country: United States
facility: MDFirst Research
state: Arizona
city: Gilbert
country: United States
facility: CCT Research - Gilbert Neurology Partners
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience, Inc.
state: Arizona
city: Anaheim
country: United States
facility: Advanced Research Center, Inc
state: California
city: Colton
country: United States
facility: Axiom Research, LLC
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center, Inc.
state: California
city: Laguna Hills
country: United States
facility: Senior Clinical Trials
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Basalt
country: United States
facility: Mountain Neurological Research Center
state: Colorado
city: Denver
country: United States
facility: Colorado Neurological Research Center, PC
state: Colorado
city: Cromwell
country: United States
facility: CT Clinical Research
state: Connecticut
city: Apopka
country: United States
facility: Topaz Clinical Research
state: Florida
city: Boca Raton
country: United States
facility: Neurology Offices of South Florida
state: Florida
city: Boynton Beach
country: United States
facility: Boynton Beach Medical Research Institute (GMI)
state: Florida
city: Clermont
country: United States
facility: K2 Medical Research - Clermont
state: Florida
city: Daytona Beach
country: United States
facility: Arrow Clinical Trials
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research - Sunrise
state: Florida
city: Jacksonville
country: United States
facility: CNS Healthcare - Jacksonville
state: Florida
city: Lady Lake
country: United States
facility: Charter Research
state: Florida
city: Lauderhill
country: United States
facility: Segal Trials - West Broward Outpatient Site
state: Florida
city: Maitland
country: United States
facility: ClinCloud
state: Florida
city: Merritt Island
country: United States
facility: Merritt Island Medical Research, LLC
state: Florida
city: Miami Beach
country: United States
facility: Quantam Clinical Trials
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I-IV INC
state: Florida
city: Miami
country: United States
facility: Central Miami Medical Institute (GMI)
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Miami
country: United States
facility: Luminous Clinical Research
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research
state: Florida
city: Orlando
country: United States
facility: Combined Research Orlando Phase I-IV
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research of Brandon, LLC (Tampa)
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: West Palm Beach
country: United States
facility: Premier Research Institute at Palm Beach Neurology
state: Florida
city: Meridian
country: United States
facility: Velocity Clinical Research, Boise
state: Idaho
city: Winfield
country: United States
facility: Northwestern Medicine Central DuPage Hospital
state: Illinois
city: Wichita
country: United States
facility: Ascension Via Christi Research
state: Kansas
city: Alexandria
country: United States
facility: Neuro Medical Clinic of Central Louisiana, LLC
state: Louisiana
city: North Dartmouth
country: United States
facility: Boston Neuro Research Center
state: Massachusetts
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Papillion
country: United States
facility: CCT Research - Papillion Research Center
state: Nebraska
city: West Long Branch
country: United States
facility: Advanced Clinical Institute, Inc
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience, Inc
state: New Mexico
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New Hyde Park
country: United States
facility: Parker Jewish Institute for Health Care & Rehabilitation
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research
state: New York
city: New York
country: United States
facility: NY Neurology Associates
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - Alzheimer's Disease Care, Research and Education Program
state: New York
city: Woodmere
country: United States
facility: Five Town Neuroscience Research
state: New York
city: Greensboro
country: United States
facility: Triad Clinical Trials, LLC
state: North Carolina
city: Matthew
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Beachwood
country: United States
facility: Insight Clinical Trials LLC
state: Ohio
city: Canton
country: United States
facility: NeuroScience Research Center, LLC
state: Ohio
city: Centerville
country: United States
facility: Dayton Center for Neurological Disorders
state: Ohio
city: Portland
country: United States
facility: Summit Research Network, LLC
state: Oregon
city: Malvern
country: United States
facility: Brian Abaluck, LLC
state: Pennsylvania
city: Moosic
country: United States
facility: Global Medical Institutes/Scranton Medical Institute - Moosic Division
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Summerville
country: United States
facility: Palmetto Clinical Research
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Austin
country: United States
facility: Senior Adults Specialty Research, Inc
state: Texas
city: Dallas
country: United States
facility: Texas Neurology, PA
state: Texas
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Katy
country: United States
facility: Mt. Olympus Medical Research, LLC
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Research Center
state: Texas
city: Rutland
country: United States
facility: Green Mountain Research Institute, Inc.
state: Vermont
city: Fairfax
country: United States
facility: Re:Cognition Health
state: Virginia
city: Seattle
country: United States
facility: Memory and Brain Wellness Center at Harborview
state: Washington
city: Macquarie Park
country: Australia
facility: KaRa MINDS
state: New South Wales
city: Herston
country: Australia
facility: The University of Queensland
state: Queensland
city: Southport
country: Australia
facility: Impact Health Pty Ltd.
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Glen Iris
country: Australia
facility: Delmont Private Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Australian Alzheimer's Research Foundation
state: Western Australia
city: London
country: Canada
facility: LMC Clinical Research - London
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Sherbrooke
country: Canada
facility: Q & T Research
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Research Sherbrooke Inc.
state: Quebec
city: Québec
country: Canada
facility: Alpha Recherche Clinique
Study officials:
affiliation: Cassava Sciences
name: James Kupiec, MD
role: STUDY_CHAIR
References: