Simufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer's Disease (REFOCUS-ALZ)

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
medical condition:
Alzheimer's Disease


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.

Study Details

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.

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.