NCT05026177 (REFOCUS-ALZ) is a Phase 3 clinical trial of Simufilam in Alzheimer Disease, sponsored by Cassava Sciences, Inc..

Who is sponsoring NCT05026177?

NCT05026177 is sponsored by Cassava Sciences, Inc..

What drugs are being tested in NCT05026177?

Interventions in NCT05026177: Simufilam, Placebo.

What condition does NCT05026177 study?

NCT05026177 studies Alzheimer Disease.

Is NCT05026177 still recruiting?

NCT05026177 is currently terminated. Last updated 22 September 2025.

Are results published for NCT05026177?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2025-09-22 · How we verify

NCT05026177: REFOCUS-ALZ

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

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

Terminated Phase 3 Results posted Last updated 22 September 2025

What this trial tests

Phase 3 trial testing Simufilam in Alzheimer Disease in 1,125 participants. Terminated before completion.

Timeline

18 November 2021

Primary endpoint
30 December 2024

30 December 2024

Quick facts

Lead sponsor	Cassava Sciences, Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	1,125
Start date	18 November 2021
Primary completion	30 December 2024
Estimated completion	30 December 2024
Sites	89 locations across Canada, United States, Puerto Rico, South Korea

Drugs / interventions tested

Simufilam — full drug profile →
Placebo

Conditions studied

Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Cassava Sciences, Inc. — full company profile →

Who can join

Adults 50 to 87, any sex, with Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Simufilam 50 mg	5.71	± 0.529
Simufilam 100 mg	5.65	± 0.509
Placebo	5.26	± 0.506

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

Group	Value	95% CI
Simufilam 50 mg	-7.20	± 0.646
Simufilam 100 mg	-6.87	± 0.623
Placebo	-5.63	± 0.620

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

Group	Value	95% CI
Simufilam 50 mg	-11.5	± 0.901
Simufilam 100 mg	-11.5	± 0.870
Placebo	-10.5	± 0.865

Change From Baseline in the Neuropsychiatric Inventory (NPI) Secondary · 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.

Group	Value	95% CI
Simufilam 50 mg	1.57	± 0.574
Simufilam 100 mg	1.44	± 0.556
Placebo	0.37	± 0.551

Change From Baseline in the MMSE Secondary · 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.

Group	Value	95% CI
Simufilam 50 mg	-3.48	± 0.288
Simufilam 100 mg	-3.29	± 0.277
Placebo	-3.35	± 0.275

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

Group	Value	95% CI
Simufilam 50 mg	1.65	± 0.186
Simufilam 100 mg	1.76	± 0.187
Placebo	1.84	± 0.186

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

Group	Value	95% CI
Simufilam 50 mg	3.37	± 0.734
Simufilam 100 mg	4.68	± 0.711
Placebo	4.40	± 0.706

Changes From Baseline in Brain Volume Via MRI Secondary · Baseline (Study Day 1) to Week 76

Changes from baseline in hippocampus, ventricles, and whole brain volume.

Whole brain volume

Group	Value	95% CI
Simufilam 50 mg	-17799.5	± 13360.83
Simufilam 100 mg	-19043.6	± 9721.20
Placebo	-17878.6	± 14012.40

Ventricular volume

Group	Value	95% CI
Simufilam 50 mg	5459.5	± 4290.67
Simufilam 100 mg	6109.9	± 3766.34
Placebo	6255.1	± 5374.61

Hippocampal volume

Group	Value	95% CI
Simufilam 50 mg	-180.7	± 109.82
Simufilam 100 mg	-192.2	± 110.23
Placebo	-186.8	± 114.54

Changes From Baseline in Amyloid Positron Emission Tomography (PET) Secondary · Baseline (Study Day 1) to Week 76

Changes from baseline in amyloid deposition in the brain.

Group	Value	95% CI
Simufilam 50 mg	0.0	± 0.10
Simufilam 100 mg	0.0	± 0.09
Placebo	0.0	± 0.09

Changes From Baseline in Tau Positron Emission Tomography (PET) Secondary · Baseline (Study Day 1) to Week 76

Changes from baseline in tau deposition in the brain

Group	Value	95% CI
Simufilam 50 mg	0.0	± 0.10
Simufilam 100 mg	0.0	± 0.07
Placebo	0.0	± 0.10

Changes From Baseline in Plasma Biomarkers Secondary · Baseline (Study Day 1) to Week 76

Change from baseline in the following plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation: phospho-tau217 (P-tau217), total tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL).

Plasma P-Tau 217

Group	Value	95% CI
Simufilam 50 mg	43.6	± 121.06
Simufilam 100 mg	4.7	± 15.74
Placebo	4.0	± 12.36

Plasma Total Tau

Group	Value	95% CI
Simufilam 50 mg	50.7	± 122.51
Simufilam 100 mg	10.9	± 41.92
Placebo	7.0	± 39.44

Plasma GFAP

Group	Value	95% CI
Simufilam 50 mg	636.5	± 1591.37
Simufilam 100 mg	235.7	± 846.47
Placebo	107.7	± 507.17

Plasma NfL

Group	Value	95% CI
Simufilam 50 mg	872.3	± 2023.12
Simufilam 100 mg	321.3	± 1397.74
Placebo	351.4	± 2075.46

Changes From Baseline in CSF Biomarkers Secondary · Baseline (Study Day 1) to Week 76

Changes from baseline in CSF biomarkers of AD pathology, neurodegeneration, and neuroinflammation: P-tau217, total tau, GFAP, and NfL.

CSF P-Tau 217

Group	Value	95% CI
Simufilam 50 mg	141.9	± 169.08
Simufilam 100 mg	90.5	± 210.38
Placebo	10.8	± 139.20

CSF Total Tau

Group	Value	95% CI
Simufilam 50 mg	136.7	± 161.10
Simufilam 100 mg	92.5	± 152.32
Placebo	28.7	± 140.48

CSF GFAP

Group	Value	95% CI
Simufilam 50 mg	1939.2	± 2409.36
Simufilam 100 mg	585.0	± 2062.91
Placebo	674.8	± 1873.18

CSF NfL

Group	Value	95% CI
Simufilam 50 mg	2372.6	± 2494.67
Simufilam 100 mg	1334.9	± 2310.62
Placebo	1535.9	± 3383.45

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 78 weeks after subjects took their first dose of study drug, or until resolution or stabilization of any AEs ongoing at the end of the study.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Simufilam 50 mg

Serious: 61/376 (16%)

Deaths: 6/376

Simufilam 100 mg

Serious: 43/374 (11%)

Deaths: 2/374

Placebo

Serious: 45/373 (12%)

Deaths: 3/373

Serious adverse events (147 terms)

Reaction	System	Simufilam 50 mg	Simufilam 100 mg	Placebo
Fall	Injury, poisoning and procedural complications	—	—	—
Syncope	Nervous system disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—
Transient ischaemic attack	Nervous system disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—
Head injury	Injury, poisoning and procedural complications	—	—	—
Upper limb fracture	Injury, poisoning and procedural complications	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—
Dementia Alzheimer's type	Nervous system disorders	—	—	—
Metabolic encephalopathy	Nervous system disorders	—	—	—
Sepsis	Infections and infestations	—	—	—
Diverticulitis	Infections and infestations	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Atrioventricular block complete	Cardiac disorders	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Asthenia	General disorders	—	—	—
Chest pain	General disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—

Other adverse events (27 terms — click to expand)

Reaction	System	Simufilam 50 mg	Simufilam 100 mg	Placebo
Fall	Injury, poisoning and procedural complications	—	—	—
COVID-19	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Dizziness	Nervous system disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Weight decreased	Investigations	—	—	—
Depression	Psychiatric disorders	—	—	—
Agitation	Psychiatric disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Fatigue	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Confusional state	Psychiatric disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Syncope	Nervous system disorders	—	—	—

Most-reported serious reactions: Fall, Syncope, Urinary tract infection, Hip fracture, Transient ischaemic attack, COVID-19, Pneumonia, Subdural haematoma.

Data from ClinicalTrials.gov NCT05026177 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Alzheimer's disease drug development pipeline: 2022.
Cummings J, Lee G, Nahed P, Kambar MEZN, et al · · 2022 · cited 369× · PMID 35516416 · DOI 10.1002/trc2.12295
Alzheimer's disease drug development pipeline: 2023.
Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2023 · cited 326× · PMID 37251912 · DOI 10.1002/trc2.12385
Alzheimer's disease drug development pipeline: 2024.
Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2024 · cited 209× · PMID 38659717 · DOI 10.1002/trc2.12465
Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.
Huang LK, Kuan YC, Lin HW, Hu CJ. · · 2023 · cited 165× · PMID 37784171 · DOI 10.1186/s12929-023-00976-6
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.
Jiang Q, Liu J, Huang S, Wang XY, et al · · 2025 · cited 74× · PMID 40059211 · DOI 10.1038/s41392-025-02145-7
Treatment of Alzheimer's Disease: Beyond Symptomatic Therapies.
Buccellato FR, D'Anca M, Tartaglia GM, Del Fabbro M, et al · · 2023 · cited 49× · PMID 37762203 · DOI 10.3390/ijms241813900
Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease.
Leuzy A, Bollack A, Pellegrino D, Teunissen CE, et al · · 2025 · cited 43× · PMID 40042435 · DOI 10.1002/alz.14528
Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis.
Tortorella I, Argentati C, Emiliani C, Morena F, et al · · 2022 · cited 26× · PMID 36231055 · DOI 10.3390/cells11193093

Verify or expand the search:

Other trials of Simufilam

Trials testing the same drug.

NCT06390410 — A Pharmacokinetic Study of Simufilam in Subjects With Impaired Hepatic Function · Phase 1 · completed
NCT06195319 — Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Simufilam Following a Single Oral Dose in Healthy · Phase 1 · completed
NCT05575076 — Open-label Extension for Phase 3 Clinical Trials of Simufilam · Phase 3 · terminated
NCT04994483 — Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease · Phase 3 · completed

Other recruiting trials for Alzheimer Disease

Currently open trials in the same condition.

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NCT06937229 — A Study to Evaluate the Long-term Efficacy and Safety of KarXT + KarX-EC for Agitation in Alzheimer's Disease (ADAGIO-3) · Phase 3 · recruiting
NCT06930560 — HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms · NA · recruiting

Other Cassava Sciences, Inc. trials

Trials by the same sponsor.

NCT06390410 — A Pharmacokinetic Study of Simufilam in Subjects With Impaired Hepatic Function · Phase 1 · completed
NCT06195319 — Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Simufilam Following a Single Oral Dose in Healthy · Phase 1 · completed
NCT05575076 — Open-label Extension for Phase 3 Clinical Trials of Simufilam · Phase 3 · terminated
NCT05352763 — Open-Label Extension of the PTI-125-04 Study in Mild-to-Moderate Alzheimer's Disease · Phase 2 · terminated
NCT04994483 — Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease · Phase 3 · completed

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT05026177 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Cassava Sciences, Inc.
Last refreshed: 22 September 2025

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05026177.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing