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REFOCUS-ALZ
TerminatedPhase 3Results postedSimufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer's Disease
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
Lead sponsor
Asset
Simufilam
Listed sites
89
Recruiting sites
-
Enrollment
1,125
actual
Study population
Alzheimer’s disease
Key I/E criterion
•MMSE 16-27
Primary endpoints
•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Drug assets
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion 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 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.
Endpoints (26)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Global cognition
4 endpointsChange From Baseline in the MMSE
Time frame:Baseline (Study Day 1) to Week 76
Mini-Mental State Examination (MMSE)
change from baseline, improvement
Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
Time frame:Baseline (Study Day 1) to Week 76
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Change From Baseline in the MMSE
Time frame:Baseline (Study Day 1) to Week 76
Mini-Mental State Examination (MMSE)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=179 Participants | -3.48 | 0.288 |
| Simufilam 100 mgn=197 Participants | -3.29 | 0.277 |
| Placebon=206 Participants | -3.35 | 0.275 |
Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
Time frame:Baseline (Study Day 1) to Week 76
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=204 Participants | 1.65 | 0.186 |
| Simufilam 100 mgn=228 Participants | 1.76 | 0.187 |
| Placebon=225 Participants | 1.84 | 0.186 |
Memory
2 endpointsChange From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
Time frame:Baseline (Study Day 1) to Week 76
ADAS-Cog
change from baseline, improvement
Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
Time frame:Baseline (Study Day 1) to Week 76
ADAS-Cog
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=167 Participants | 5.71 | 0.529 |
| Simufilam 100 mgn=181 Participants | 5.65 | 0.509 |
| Placebon=188 Participants | 5.26 | 0.506 |
Function / daily living
2 endpointsChange From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time frame:Baseline (Study Day 1) to Week 76
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time frame:Baseline (Study Day 1) to Week 76
ADCS-Activities of Daily Living (ADCS-ADL)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=169 Participants | -7.20 | 0.646 |
| Simufilam 100 mgn=179 Participants | -6.87 | 0.623 |
| Placebon=187 Participants | -5.63 | 0.620 |
Behavior / neuropsychiatric
2 endpointsChange From Baseline in the Neuropsychiatric Inventory (NPI)
Time frame:Baseline (Study Day 1) to Week 76
Neuropsychiatric Inventory (NPI)
change from baseline, improvement
Change From Baseline in the Neuropsychiatric Inventory (NPI)
Time frame:Baseline (Study Day 1) to Week 76
Neuropsychiatric Inventory (NPI)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=176 Participants | 1.57 | 0.574 |
| Simufilam 100 mgn=191 Participants | 1.44 | 0.556 |
| Placebon=199 Participants | 0.37 | 0.551 |
Amyloid biomarkers
2 endpointsChanges From Baseline in Amyloid Positron Emission Tomography (PET)
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Changes From Baseline in Amyloid Positron Emission Tomography (PET)
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Posted result
| Group | Value (mean), µL | Standard deviation |
|---|---|---|
| Simufilam 50 mgn=31 Participants | 0.0 | 0.10 |
| Simufilam 100 mgn=19 Participants | 0.0 | 0.09 |
| Placebon=27 Participants | 0.0 | 0.09 |
Tau biomarkers
4 endpointsChanges From Baseline in Plasma Biomarkers
Time frame:Baseline (Study Day 1) to Week 76
Phosphorylated tau 217 (p-tau217)
change from baseline, improvement
Changes From Baseline in CSF Biomarkers
Time frame:Baseline (Study Day 1) to Week 76
Phosphorylated tau 217 (p-tau217)
ratio, descriptive
Changes From Baseline in Plasma Biomarkers
Time frame:Baseline (Study Day 1) to Week 76
Phosphorylated tau 217 (p-tau217)
change from baseline, improvement
Posted result
| Group | Value (mean), pg/mL | Standard deviation |
|---|---|---|
| Simufilam 50 mgPlasma P-Tau 217n=47 Participants | 43.6 | 121.06 |
| Plasma Total Taun=47 Participants | 50.7 | 122.51 |
| Plasma GFAPn=47 Participants | 636.5 | 1591.37 |
| Plasma NfLn=47 Participants | 872.3 | 2023.12 |
| Simufilam 100 mgPlasma P-Tau 217n=27 Participants | 4.7 | 15.74 |
| Plasma Total Taun=27 Participants | 10.9 | 41.92 |
| Plasma GFAPn=27 Participants | 235.7 | 846.47 |
| Plasma NfLn=27 Participants | 321.3 | 1397.74 |
| PlaceboPlasma P-Tau 217n=41 Participants | 4.0 | 12.36 |
| Plasma Total Taun=41 Participants | 7.0 | 39.44 |
| Plasma GFAPn=41 Participants | 107.7 | 507.17 |
| Plasma NfLn=41 Participants | 351.4 | 2075.46 |
Changes From Baseline in CSF Biomarkers
Time frame:Baseline (Study Day 1) to Week 76
Phosphorylated tau 217 (p-tau217)
ratio, descriptive
Posted result
| Group | Value (mean), pg/mL | Standard deviation |
|---|---|---|
| Simufilam 50 mgCSF P-Tau 217n=21 Participants | 141.9 | 169.08 |
| CSF Total Taun=21 Participants | 136.7 | 161.10 |
| CSF GFAPn=21 Participants | 1939.2 | 2409.36 |
| CSF NfLn=21 Participants | 2372.6 | 2494.67 |
| Simufilam 100 mgCSF P-Tau 217n=14 Participants | 90.5 | 210.38 |
| CSF Total Taun=14 Participants | 92.5 | 152.32 |
| CSF GFAPn=14 Participants | 585.0 | 2062.91 |
| CSF NfLn=14 Participants | 1334.9 | 2310.62 |
| PlaceboCSF P-Tau 217n=19 Participants | 10.8 | 139.20 |
| CSF Total Taun=19 Participants | 28.7 | 140.48 |
| CSF GFAPn=19 Participants | 674.8 | 1873.18 |
| CSF NfLn=19 Participants | 1535.9 | 3383.45 |
Neuroimaging
2 endpointsChanges From Baseline in Brain Volume Via MRI
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Changes From Baseline in Brain Volume Via MRI
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Posted result
| Group | Value (mean), µL | Standard deviation |
|---|---|---|
| Simufilam 50 mgWhole brain volumen=52 Participants | -17799.5 | 13360.83 |
| Ventricular volumen=52 Participants | 5459.5 | 4290.67 |
| Hippocampal volumen=52 Participants | -180.7 | 109.82 |
| Simufilam 100 mgWhole brain volumen=48 Participants | -19043.6 | 9721.20 |
| Ventricular volumen=48 Participants | 6109.9 | 3766.34 |
| Hippocampal volumen=48 Participants | -192.2 | 110.23 |
| PlaceboWhole brain volumen=50 Participants | -17878.6 | 14012.40 |
| Ventricular volumen=50 Participants | 6255.1 | 5374.61 |
| Hippocampal volumen=50 Participants | -186.8 | 114.54 |
Fluid / digital biomarkers
2 endpointsChange From Baseline in Plasma Biomarker SavaDx
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Change From Baseline in Plasma Biomarker SavaDx
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Caregiver / quality of life
2 endpointsChange From Baseline in the Zarit Burden Interview (ZBI)
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Change From Baseline in the Zarit Burden Interview (ZBI)
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=169 Participants | 3.37 | 0.734 |
| Simufilam 100 mgn=180 Participants | 4.68 | 0.711 |
| Placebon=185 Participants | 4.40 | 0.706 |
Other (unclassified)
4 endpointsChange From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)
Time frame:Baseline (Study Day 1) to Week 76
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), score on a scale | Standard error |
|---|---|---|
| Simufilam 50 mgn=167 Participants | -11.5 | 0.901 |
| Simufilam 100 mgn=177 Participants | -11.5 | 0.870 |
| Placebon=185 Participants | -10.5 | 0.865 |
Changes From Baseline in Tau Positron Emission Tomography (PET)
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Changes From Baseline in Tau Positron Emission Tomography (PET)
Time frame:Baseline (Study Day 1) to Week 76
descriptive
Posted result
| Group | Value (least_squares_mean), µL | Standard error |
|---|---|---|
| Simufilam 50 mgn=27 Participants | 0.0 | 0.10 |
| Simufilam 100 mgn=14 Participants | 0.0 | 0.07 |
| Placebon=23 Participants | 0.0 | 0.10 |
Publications (1)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- PMID41500915via DERIVED
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.