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CompletedPhase 2Results posted

PTI-125 for Mild-to-moderate Alzheimer's Disease Patients

A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multiple Dose, Biomarker and Safety Study of PTI-125 in Mild-to-moderate Alzheimer's Disease Patients

Asset

Simufilam

Listed sites

9

Recruiting sites

-

Enrollment

64

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 16-26•Study partner/caregiver required•Background AD symptomatic therapy, if used: stable ≥3 months

Primary endpoints

•CSF Abeta42•CSF Total Tau•Phosphorylated tau 181 (p-tau181)

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

NCT IDNCT04079803
Org study IDPTI-125-02

Timeline

Milestones

Study first posted2019-09-06actual
Study start2019-09-09actual
Primary completion2020-03-31actual
Study completion2020-03-31actual
Results first posted2021-06-01actual
Last update posted2021-09-29actual

Assets

Drug assets

Simufilam

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years
Maximum age85 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

•Ages >= 50 and <= 85 years
•Informed consent form (ICF) signed by the subject or legally acceptable representative.
•Clinical diagnosis of dementia due to possible or probable Alzheimer's disease
•Mini-Mental State Examination score >= 16 and <= 26 at screening
•If female, postmenopausal for at least 1 year
•Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care
•General health status acceptable for participation in the study
•Fluency (oral and written) in English or Spanish
•If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months. If receiving donepezil, any dose lower than 23 mg once daily.
•The patient is a non-smoker for at least 3 years.
•The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.
•The patient has a ratio of total tau/Aβ42 in cerebrospinal fluid >= 0.28.
•Patient has a caregiver or legal representative responsible for administering the drug and recording the time

Exclusion criteria

•Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening
•Enrollment in the previous PTI-125 trial
•A medical condition that would interfere with a lumbar puncture
•Residence in a skilled nursing facility and requiring 24 h care.
•Clinically significant laboratory test results
•Clinically significant untreated hypothyroidism
•Insufficiently controlled diabetes mellitus
•Renal insufficiency (serum creatinine > ULN)
•Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)
•History of ischemic colitis or ischemic enterocolitis
•Unstable medical condition that is clinically significant in the judgment of the investigator
•Alanine transaminase (ALT) or aspartate transaminase (AST) > ULN or total bilirubin > ULN.
•History of myocardial infarction or unstable angina within 6 months before screening
•History of more than 1 myocardial infarction within 5 years before screening
•Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
•Symptomatic hypotension, or uncontrolled hypertension
•Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT interval value >= 450 msec for males or >= 470 msec for females.
•Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
•History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
•Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
•Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
•Specific degenerative Central Nervous System disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
•Wernicke's encephalopathy
•Active acute or chronic Central Nervous System infection
•Donepezil 23 mg quaque die currently or within 3 months prior to randomization
•Discontinued AChEI < 30 days prior to randomization
•Antipsychotics; low doses are allowed only if the subject has received a stable dose for at least 3 months before randomization
•Tricyclic antidepressants and monoamine oxidase inhibitors
•Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed
•Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
•Antiepileptic medications if taken for control of seizures
•Chronic intake of opioid-containing analgesics
•Sedating H1 antihistamines
•Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
•Clinically significant illness within 30 days of enrollment
•History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
•Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus HCV antibody test at screening
•Positive HIV test at screening
•Positive urine drug test at screening
•Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
•Suicidality on C-SSRS at screening

Endpoints (24)

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

Fluid / digital biomarkers
8
Neurodegeneration biomarkers
4
Other (unclassified)
4
Global cognition
2
Memory
2
Amyloid biomarkers
2
Tau biomarkers
2

Global cognition

2 endpoints
Secondary/protocol endpoint

Spatial Working Memory Test

Time frame:Day 1 to Day 28

event count, event

Secondary/registry result

Spatial Working Memory Test

Time frame:Day 1 to Day 28

event count, event

Posted result

GroupValue (mean), Change from Day 1 in total errorsStandard deviation
Placebo Cohortn=22 Participants-0.417.54
Simufilam (PTI-125), 100 mg Tablets Cohortn=18 Participants-2.317.45
Simufilam (PTI-125), 50 mg Tablets Cohortn=17 Participants-3.354.86
Effect size0.46

This study was not powered for statistical significance on cognitive measures.

Effect size0.25

This study was not powered for statistical significance on cognitive measures.

Memory

2 endpoints
Secondary/protocol endpoint

Paired Associates Learning Test

Time frame:Day 1 to Day 28

event count, event

Secondary/registry result

Paired Associates Learning Test

Time frame:Day 1 to Day 28

event count, event

Posted result

GroupValue (mean), Change from Day 1 in total errorsStandard deviation
Placebo Cohortn=14 Participants-1.58.5
Simufilam (PTI-125), 100 mg Tablets Cohortn=13 Participants-4.517.7
Simufilam (PTI-125), 50 mg Tablets Cohortn=10 Participants-5.713.6
Effect size0.23

This study was not powered for statistical significance on cognitive measures.

Effect size0.37

This study was not powered for statistical significance on cognitive measures.

Amyloid biomarkers

2 endpoints
Primary/protocol endpoint

Change From Baseline in CSF Abeta42

Time frame:Screening to Day 28

change from baseline, improvement

Primary/registry result

Change From Baseline in CSF Abeta42

Time frame:Screening to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants4.830.9
Simufilam (PTI-125), 100 mg Tablets Cohortn=21 Participants12.511.9
Simufilam (PTI-125), 50 mg Tablets Cohortn=19 Participants16.221.1
p0.087ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.01ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Tau biomarkers

2 endpoints
Primary/protocol endpoint

Change From Baseline in CSF Total Tau.

Time frame:Screening to Day 28

change from baseline, improvement

Primary/registry result

Change From Baseline in CSF Total Tau.

Time frame:Screening to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants-3.214.8
Simufilam (PTI-125) 100 mg Tablets Cohortn=21 Participants-18.710.4
Simufilam (PTI-125) 50 mg Tablets Cohortn=19 Participants-14.69.6
p<0.0001ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.0012ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Neurodegeneration biomarkers

4 endpoints
Primary/protocol endpoint

Change From Baseline in CSF Neurogranin

Time frame:Screening to Day 28

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in CSF Neurofilament Light Chain

Time frame:Screening to Day 28

Neurofilament light (NfL)

change from baseline, improvement

Primary/registry result

Change From Baseline in CSF Neurogranin

Time frame:Screening to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants-50.5434
Simufilam (PTI-125), 100 mg Tablets Cohortn=21 Participants-648491
Simufilam (PTI-125), 50 mg Tablets Cohortn=19 Participants-527361
p0.0002ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.0005ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Primary/registry result

Change From Baseline in CSF Neurofilament Light Chain

Time frame:Screening to Day 28

Neurofilament light (NfL)

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants-10.045
Simufilam (PTI-125), 100 mg Tablets Cohortn=21 Participants-76.350.6
Simufilam (PTI-125), 50 mg Tablets Cohortn=19 Participants-49.735.5
p0.0003ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.0058ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Fluid / digital biomarkers

8 endpoints
Primary/protocol endpoint

Change From Baseline in CSF P-tau181

Time frame:Screening to Day 28

Phosphorylated tau 181 (p-tau181)

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in CSF YKL-40

Time frame:Screening to Day 28

change from baseline, improvement

Primary/registry result

Change From Baseline in CSF P-tau181

Time frame:Screening to Day 28

Phosphorylated tau 181 (p-tau181)

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants-0.631.8
Simufilam (PTI-125), 100 mg Tablets Cohortn=21 Participants-3.11.7
Simufilam (PTI-125), 50 mg Tablets Cohortn=19 Participants-2.41.6
p0.005ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.002ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Primary/registry result

Change From Baseline in CSF YKL-40

Time frame:Screening to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), pg/mLStandard deviation
Placebo Cohortn=22 Participants-0.9624.2
Simufilam (PTI-125), 100 mg Tablets Cohortn=21 Participants-22.311.7
Simufilam (PTI-125), 50 mg Tablets Cohortn=19 Participants-20.417.4
p0.0001ANCOVA

This primary analysis includes two 100 mg subjects who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

p0.0001ANCOVA

This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Secondary/protocol endpoint

CSF IL-6, sTREM2, HMGB1, Albumin, IgG

Time frame:Screening to Day 28

change from baseline, improvement

Secondary/registry result

CSF IL-6, sTREM2, HMGB1, Albumin, IgG

Time frame:Screening to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), pg/mL; optical density for albumin & IgGStandard deviation
Placebo CohortCSF IL-6n=22 Participants-1.12.0
CSF sTREM2n=22 Participants-77.3510
CSF HMGB1n=22 Participants19.4172.3
CSF albuminn=22 Participants-2401620
CSF IgGn=22 Participants-574.82518
Simufilam (PTI-125), 100 mg Tablets CohortCSF IL-6n=19 Participants-3.71.8
CSF sTREM2n=19 Participants-426274
CSF HMGB1n=19 Participants-14351.3
CSF albuminn=19 Participants-22921760
CSF IgGn=19 Participants-23502517
Simufilam (PTI-125), 50 mg Tablets CohortCSF IL-6n=18 Participants-3.31.9
CSF sTREM2n=18 Participants-424386
CSF HMGB1n=18 Participants-15250.1
CSF albuminn=18 Participants-12451735
CSF IgGn=18 Participants-24442097
p0.0078ANCOVA

This analysis is for IL-6.

p0.019ANCOVA

This analysis is for IL-6.

p0.0002ANCOVA

This analysis is for sTREM2.

p0.0007ANCOVA

This analysis is for sTREM2.

p0.0001ANCOVA

This analysis is for HMGB1.

p0.0001ANCOVA

This analysis is for HMGB1.

p0.0001ANCOVA

This analysis is for albumin.

p0.046ANCOVA

This analysis is for albumin.

p0.012ANCOVA

This analysis is for Immunoglobulin G.

p0.014ANCOVA

This analysis is for Immunoglobulin G.

Other/protocol endpoint

Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker

Time frame:Day 1 to Day 28

percent change from baseline, improvement

Other_pre_specified/registry result

Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker

Time frame:Day 1 to Day 28

percent change from baseline, improvement

Posted result

GroupValue (mean), Percent changeStandard deviation
Placebo Cohortn=22 Participants-3.262
Simufilam (PTI-125), 100 mg Tablets Cohortn=19 Participants-47.819
Simufilam (PTI-125), 50 mg Tablets Cohortn=17 Participants-44.135
p0.003ANOVA
p0.016ANOVA

Other (unclassified)

4 endpoints
Other/protocol endpoint/low confidence

Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes

Time frame:Day 1 to Day 28

change from baseline, improvement

Other/protocol endpoint/low confidence

Plasma P-tau181

Time frame:Day 1 to Day 28

Phosphorylated tau 181 (p-tau181)

percent change from baseline, improvement

Other_pre_specified/registry result/low confidence

Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes

Time frame:Day 1 to Day 28

change from baseline, improvement

Posted result

GroupValue (mean), ratio to total FLNAStandard deviation
Placebo CohortFLNA - alpha7nAChR linkagen=22 Participants-0.070.19
FLNA - TLR4 linkagen=22 Participants-0.050.18
Simufilam (PTI-125), 100 mg Tablets CohortFLNA - alpha7nAChR linkagen=19 Participants-0.240.16
FLNA - TLR4 linkagen=19 Participants-0.190.14
Simufilam (PTI-125), 50 mg Tablets CohortFLNA - alpha7nAChR linkagen=17 Participants-0.230.13
FLNA - TLR4 linkagen=17 Participants-0.190.11
p0.005ANOVA
p0.009ANOVA
p0.01ANOVA
p0.01ANOVA
Other_pre_specified/registry result/low confidence

Plasma P-tau181

Time frame:Day 1 to Day 28

Phosphorylated tau 181 (p-tau181)

percent change from baseline, improvement

Posted result

GroupValue (mean), Percent changeStandard deviation
Placebo Cohortn=20 Participants20.749
Simufilam (PTI-125) 100 mg Tablets Cohortn=17 Participants-16.529
Simufilam (PTI-125) 50 mg Tablets Cohortn=15 Participants-15.136
p0.01ANOVA
p0.02ANOVA
p0.009ANOVA

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

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableClinicalTrials.gov results section

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.