Simufilam (PTI-125), 100 mg, for Mild-to-moderate Alzheimer's Disease Patients (PTI-125)

April 21, 2025 updated by: Cassava Sciences, Inc.

A 12-Month, Open-Label Safety Study of Simufilam Followed by a 6-Month Randomized Withdrawal and 6 Additional Months Open-Label in Mild-to-moderate Alzheimer's Disease Patients

A two-year safety study of simufilam (PTI-125) 100 mg oral tablets twice daily for participants of the previous simufilam studies as wells as additional new mild-to-moderate Alzheimer's disease subjects for a total of 200 participants. All participants will receive simufilam 100 mg tablets twice daily for one year, followed by a 6-month randomized, double-blind period where subjects will either continue on active treatment or be switched to placebo. The study concludes with an additional 6-month open-label treatment period. Clinic visits are every month or month and a half in the first year, and every 3 months in the second year with an additional visit at Month 13. Cognition and neuropsychiatric symptoms are evaluated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The objectives of this study are to build the safety database for simufilam (PTI-125) and to investigate its effects on biomarkers, cognition and neuropsychiatric symptoms during 12-month twice-daily administration in mild-to-moderate AD patients. Additional objectives are to assess differences in cognition and neuropsychiatric symptoms between active and placebo arms in the 6-month randomized period. All subjects will undergo lumbar puncture at screening for baseline testing of cerebrospinal fluid (CSF) total tau and Abeta42, and the first 50 subjects will also provide a CSF sample at Month 6 or Month 12 for evaluation of change from baseline in CSF biomarkers. CSF will not be required of subjects with prior CSF, PET or MRI evidence of Alzheimer's disease. Plasma biomarkers will be evaluated in all subjects. Safety will be assessed by blood tests, electrocardiograms, adverse event monitoring and, at Months 12 and 24, full physical examinations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
220

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Z 1G3
        • Ottawa Memory Clinic
      • Toronto, Ontario, Canada, M3B 2S7
        • Toronto Memory Program
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85296
        • Cognitive Clinical Trials
      • Surprise, Arizona, United States, 85374
        • Cognitive Clinical Trials
    • California
      • Imperial, California, United States, 92251
        • Sun Valley Research Center, Inc.
    • Florida
      • Delray Beach, Florida, United States, 33445
        • Brain Matters Research
      • Fort Myers, Florida, United States, 33912
        • Neuropsychiatric Research Center of Southwest Florida
      • Miami, Florida, United States, 33125
        • Optimus U
      • Miami Lakes, Florida, United States, 33016
        • Adaptive Clinical Research, Inc
      • Palmetto Bay, Florida, United States, 33157
        • IMIC, Inc.
    • Nebraska
      • Bellevue, Nebraska, United States, 68005
        • Cognitive Clinical Trials
      • Omaha, Nebraska, United States, 68130
        • Cognitive Clinical Trials
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Advanced Memory Research Institute
    • Ohio
      • North Canton, Ohio, United States, 44720
        • Neuro-Behavioral Clinical Research
    • Texas
      • Austin, Texas, United States, 78757
        • Senior Adults Specialty Research
      • Houston, Texas, United States, 77058
        • Centex Studies, Inc.
      • McAllen, Texas, United States, 78504
        • Centex Studies

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA:

  1. Informed consent form (ICF) signed by the subject or legally acceptable representative.
  2. Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
  3. Ages ≥ 50 and ≤ 85 years
  4. Clinical diagnosis of dementia due to possible or probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer's Disease Association.
  5. If female, postmenopausal for at least 1 year
  6. Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-h) nursing care
  7. General health status acceptable for participation in the study
  8. Fluency (oral and written) in English or Spanish
  9. If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months (90 days) before screening. If receiving donepezil, receiving any dose lower than 23 mg once daily. Multiple medications are allowed.
  10. The patient is a non-smoker for at least 3 years.
  11. The patient or legal representative must agree to comply with the drawing of blood samples for the PK assessments, laboratory assessments and SavaDx.
  12. MMSE-2 score ≥ 16 and ≤ 26 at screening, OR if > 26, must have evidence of AD pathology such as a prior CSF total tau/Aβ42 ratio ≥ 0.28, an amyloid positive PET scan or hippocampal volume loss consistent with AD.

EXCLUSION CRITERIA:

  1. Anything that in the opinion of the Investigator would preclude participation in a 2-year study.
  2. BMI < 18.5
  3. Positive urine drug screen.
  4. Positive HIV, HCV or HbsAg screen.
  5. Suicidality on C-SSRS
  6. Exposure to an experimental drug other than simufilam, experimental biologic or experimental medical device within 3 months before screening
  7. A medical condition that would interfere with a lumbar puncture
  8. Residence in a skilled nursing facility and requiring 24 h care.
  9. Clinically significant laboratory test results
  10. Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
  11. Insufficiently controlled diabetes mellitus, including requiring insulin or metformin >1000 mg/day.
  12. Renal insufficiency (serum creatinine > ULN and clinically significant in the opinion of PI and/or Sponsor OR eGFR <60 ml/min/m2 as estimated by either the MDRD or CKD-EPI equation)
  13. 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)
  14. History of ischemic colitis or ischemic enterocolitis
  15. Unstable medical condition that is clinically significant in the judgment of the investigator
  16. Alanine transaminase (ALT) or aspartate transaminase (AST) > ULN or total bilirubin > ULN and clinically significant in the opinion of PI and/or Sponsor.
  17. History of myocardial infarction or unstable angina within 6 months before screening
  18. History of more than 1 myocardial infarction within 5 years before screening
  19. Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)
  20. Symptomatic hypotension, or uncontrolled hypertension
  21. Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed QTc (Fridericia correction method) value ≥ 450 msec for males or ≥ 470 msec for females.
  22. Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia
  23. History of brain tumor or other clinically significant space-occupying lesion on CT or MRI
  24. Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia
  25. Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation
  26. Specific degenerative CNS disease diagnosis other than AD (e.g., Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
  27. Wernicke's encephalopathy
  28. Active acute or chronic CNS infection
  29. Donepezil 23 mg or greater QD currently or within 3 months prior to randomization
  30. Discontinued AChEI < 30 days prior to randomization
  31. Antipsychotics; low doses are allowed only if given for sleep disturbances, agitation and/or aggression, and only if the subject has received a stable dose for at least 3 months before randomization
  32. Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants are allowed only if the subject has received a stable dose for at least 3 months before randomization
  33. Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before randomization
  34. Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)
  35. Antiepileptic medications if taken for control of seizures
  36. Chronic intake of opioid-containing analgesics
  37. Sedating H1 antihistamines
  38. Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
  39. Clinically significant illness within 30 days of enrollment
  40. History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
  41. Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
  42. COVID-19 infection within 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Simufilam 100 mg oral tablets throughout
Simufilam 100 mg oral tablets administered twice daily (BID) for the full 24 months (including the randomized period Month 12 to Month 18)
Drug: Simufilam 100 mg oral tablet
Simufilam 100 mg oral tablet for b.i.d. administration
Other Names:
  • PTI-125
  • Sumifilam
Placebo Comparator: Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets
This placebo arm is only for Month 12 to Month 18. Day 1 to Month 12, as well as Month 18 to Month 24 are open-label treatment periods of simufilam 100 mg b.i.d. for all subjects.
Drug: Simufilam 100 mg oral tablet
Simufilam 100 mg oral tablet for b.i.d. administration
Other Names:
  • PTI-125
  • Sumifilam
Drug: Placebo
Matching placebo oral tablets

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in ADAS-Cog-11
Time Frame: Day 1 to Month 24
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition over the course of 24 months Possible range in score: 0-70; Subscales are summed; Higher values represent a more cognitively impaired participant Decrease in mean value represents improvement in cognition from one timepoint to the next.
Day 1 to Month 24
Change From Baseline in ADAS-Cog-11 (Month 12 to Month 24)
Time Frame: Month 12 to Month 24
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition Starting at month 12 through month 24; Possible range in score: 0-70; Higher values represent a more cognitively impaired participant; Decrease in mean value represents improvement in cognition from one timepoint to the next.
Month 12 to Month 24
Safety and Tolerability (Open Label Abnormal Vital Signs)
Time Frame: Day 1 to Month 12 and month 18 to month 24
The most frequently reported Treatment Emergent Adverse Events indicative of abnormal vital signs (hypertension/worsening of hypertension and blood pressure increase) of simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Vital Signs)
Time Frame: Month 12 to month 18
The most frequently reported Treatment Emergent Adverse Event indicative of abnormal vital signs (hypotension) of simufilam (PTI-125) or placebo during the randomized withdraw portion of the study : Month 12 to Month 18
Month 12 to month 18
Safety and Tolerability (Open Label Electrocardiogram Results)
Time Frame: Day 1 to Month 12 and month 18 to month 24
The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Electrocardiogram Results)
Time Frame: Month 12 to Month 18
The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Physical Examination)
Time Frame: Day 1 to Month 12 and month 18 to month 24
The most frequently reported Treatment Emergent Adverse Events indicative of abnormal physical examination (weight increase or weight decrease) while administered simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Physical Examination Findings)
Time Frame: Month 12 to Month 18
The number of subjects that had Treatment Emergent Adverse Events of indicative of abnormal physical examination while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Clinical Laboratory Results)
Time Frame: Day 1 to Month 12 and month 18 to month 24
Treatment Emergent Adverse Events when three or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Clinical Laboratory Results)
Time Frame: Month 12 to Month 18
Treatment Emergent Adverse Events when two or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
Month 12 to Month 18

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Mean Concentration (pg/mL)
Time Frame: Day 1 to Month 12
Change from baseline to month 12 in Cerebral Spinal Fluid for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Mean Concentration (pg/mL) (samples stored at -70 degrees Celsius; assays performed at Abilene Christian University Bioanalytics Laboratory)
Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Tau Protein Mean Concentration (pg/mL)
Time Frame: Day 1 to Month 12
Change from baseline to month 12 in Cerebral Spinal Fluid for Tau Protein Mean Concentration (pg/mL) (samples stored at -70 degrees Celsius; assays performed at Abilene Christian University Bioanalytics Laboratory)
Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurogranin Mean Concentration (pg/mL)
Time Frame: Day 1 to Month 12
Change from baseline to month 12 in Cerebral Spinal Fluid for Neurogranin Mean Concentration (pg/mL) (samples stored at -70 degrees Celsius; assays performed at Abilene Christian University Bioanalytics Laboratory)
Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurofilament Light Chain Protein Mean Concentration (pg/mL)
Time Frame: Day 1 to Month 12
Change from baseline to month 12 in Cerebral Spinal Fluid for Neurofilament Light Chain Protein Mean Concentration (pg/mL) (samples stored at -70 degrees Celsius; assays performed at Abilene Christian University Bioanalytics Laboratory)
Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Glial Fibrillary Acidic Protein Mean Concentration (pg/mL)
Time Frame: Day 1 to Month 12
Change from baseline to month 12 in Cerebral Spinal Fluid for Glial Fibrillary Acidic Protein Mean Concentration (pg/mL) (samples stored at -70 degrees Celsius; assays performed at Abilene Christian University Bioanalytics Laboratory)
Day 1 to Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cassava Sciences, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Lindsay Burns, PhD, Cassava Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 9, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 9, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 14, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PTI-125-04
  • R44AG065152 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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