Simufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer's Disease

NCT05026177
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Phase
Phase 3
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Recruitment status
Terminated
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Participants
1,125
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Lead sponsor
Cassava Sciences, Inc.
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Start date
2021-11-18
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Number of sites
89
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Summary
A 76-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 76 weeks. Approximately 1083 participants will be randomized (1:1:1) to receive either placebo, 50 mg tablets of simufilam, or 100 mg tablets of simufilam, twice daily, for 76 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.
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Acronym
REFOCUS-ALZ
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Short title
Simufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer's Disease
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Official title
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, 76-week Study Evaluating the Safety and Efficacy of Two Doses of Simufilam in Subjects With Mild-to-Moderate Alzheimer's Disease
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Control arm
Placebo
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Terminated
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Phase
Phase 3
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Study type
Interventional
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Reason stopped
Sponsor decision
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Completion date
2024-12-30
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First posted
2021-08-30
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Registry last updated
2025-09-22
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Primary completion date
2024-12-30
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Start date
2021-11-18
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Actual participants
1,125
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Participants
1,125
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Participant count basis
Actual
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Protocol amendments
6
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Randomisation ratio
1:1:1
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Number of sites
89
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Cassava Sciences, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05026177
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ClinicalTrials.gov ID
NCT05026177
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masking description
Randomized treatments will be assigned by subject numbers in a randomly generated numeric sequence. Randomization (1:1:1) 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.
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

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

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 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).

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

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 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 for the subject. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.

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

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.

  2. Change From Baseline in the Neuropsychiatric Inventory (NPI)

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 in the NPI, a 12-item study partner interview, which records the frequency and severity of common neuropsychiatric symptoms in dementia for the subject, as well as the level of study partner distress due to the neuropsychiatric problems. Scores range from 0 to 144, with higher scores indicating more frequent and severe symptoms, and greater levels of partner distress.

  3. Change From Baseline in the MMSE

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 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. Scores range from 0 to 30; lower scores indicate more severe impairment.

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

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 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. Scores for each domain have a minimum of 0 and a maximum of 3, and the 6 domain scores are summed to give the CDR-SB, which has a minimum score of 0 and a maximum score of 18. Higher scores indicate more severe impairment.

  5. Change From Baseline in the Zarit Burden Interview (ZBI)

    Timeframe: Baseline (Study Day 1) to Week 76

    The change from baseline to Week 76 in the ZBI, a 22-item study partner questionnaire designed to assess the stress or burden experienced by caregivers of people with dementia. Scores range from 0 to 88, with a higher score indicating greater stress or burden.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
50 Years
Maximum age
87 Years
Healthy volunteers
No

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 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.
Sources for eligibility
clinicaltrials.gov

  • Banner Alzheimer's InstitutePhoenix, United States
  • Arizona Neuroscience Research, LLCPhoenix, United States
  • Clinical EndpointsScottsdale, United States
  • Banner Sun Health Research InstituteSun City, United States
  • Banner Alzheimer's Institute - TucsonTucson, United States
  • North County Neurology AssociatesCarlsbad, United States
  • Neuro-Pain Medical CenterFresno, United States
  • Neurology Center of North Orange CountyFullerton, United States
  • Healthy Brain ClinicLong Beach, United States
  • California Research InsituteLos Angeles, United States
  • Shankle Clinic and Hoag Memorial Hospital PresbyterianNewport Beach, United States
  • Pacific Research Network, LLCSan Diego, United States
  • Nuvance Health Medical Practice CT, Inc. - Associated Neurologists, PCDanbury, United States
  • Ki Health Partners, LLCStamford, United States
  • JEM Research InstituteAtlantis, United States
  • Parkinson's Disease and Movement Disorders Center of Boca RatonBoca Raton, United States
  • Clinical Research of Brandon, LLCBrandon, United States
  • Quantum LaboratoriesDeerfield Beach, United States
  • Brain Matters Research IncDelray Beach, United States
  • Indago Research and Health Center, Inc.Hialeah, United States
  • Alphab Global ResearchJupiter, United States
  • K2 Medical ResearchMaitland, United States
  • Mind Institute at Miami Jewish HealthMiami, United States
  • Brainstorm ResearchMiami, United States
  • Health Synergy Clinical ResearchOkeechobee, United States

And 64 more, listed on the interactive page.

Sources for sites
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Sources for references
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Related records

Drugs (1)

Collaborators (1)

Lead sponsors (1)

Conditions (1)

Targets (1)