Alzheimer DiseasePhase 2PTI-125NCT04388254
Simufilam (PTI-125), 100 mg, for Mild-to-moderate Alzheimer's Disease Patients
A Phase 2 study testing Simufilam 100 mg oral tablet in people with Alzheimer Disease, run by Cassava Sciences, Inc. at 17 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Simufilam 100 mg oral tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 24 Mar 2020to 9 Nov 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent form (ICF) signed by the subject or legally acceptable representative.
- Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
- Ages ≥ 50 and ≤ 85 years
- 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.
- 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
Show all 12Show fewer
- 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 (90 days) before screening. If receiving donepezil, receiving any dose lower than 23 mg once daily. Multiple medications are allowed.
- 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 for the PK assessments, laboratory assessments and SavaDx.
- 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.
Who cannot join
- Anything that in the opinion of the Investigator would preclude participation in a 2-year study.
- BMI < 18.5
- Positive urine drug screen.
- Positive HIV, HCV or HbsAg screen.
- Suicidality on C-SSRS
- Exposure to an experimental drug other than simufilam, experimental biologic or experimental medical device within 3 months before screening
Show all 42Show fewer
- 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 (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)
- Insufficiently controlled diabetes mellitus, including requiring insulin or metformin >1000 mg/day.
- 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)
- 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 and clinically significant in the opinion of PI and/or Sponsor.
- 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 QTc (Fridericia correction method) 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 CNS disease diagnosis other than AD (e.g., Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)
- Wernicke's encephalopathy
- Active acute or chronic CNS infection
- Donepezil 23 mg or greater QD currently or within 3 months prior to randomization
- Discontinued AChEI < 30 days prior to randomization
- 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
- 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
- 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
- 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
- Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study
- COVID-19 infection within 3 months
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States15 sites
Senior Adults Specialty Research
Austin, Texas, 78757
Cognitive Clinical Trials
Bellevue, Nebraska, 68005
Brain Matters Research
Delray Beach, Florida, 33445
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, 33912
Cognitive Clinical Trials
Gilbert, Arizona, 85296
Centex Studies, Inc.
Houston, Texas, 77058
Sun Valley Research Center, Inc.
Imperial, California, 92251
Centex Studies
McAllen, Texas, 78504
Optimus U
Miami, Florida, 33125
Adaptive Clinical Research, Inc
Miami Lakes, Florida, 33016
Neuro-Behavioral Clinical Research
North Canton, Ohio, 44720
Cognitive Clinical Trials
Omaha, Nebraska, 68130
IMIC, Inc.
Palmetto Bay, Florida, 33157
Cognitive Clinical Trials
Surprise, Arizona, 85374
Advanced Memory Research Institute
Toms River, New Jersey, 08755
Canada2 sites
Ottawa Memory Clinic
Ottawa, Ontario, K1Z 1G3
Toronto Memory Program
Toronto, Ontario, M3B 2S7
About this study
Official title: 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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Simufilam 100 mg oral tablet, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simufilam 100 mg oral tabletDrug
Also called PTI-125, Sumifilam
Simufilam 100 mg oral tablet for b.i.d. administration
PlaceboDrug
Matching placebo oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Simufilam 100 mg oral tablets throughout | Experimental | Simufilam 100 mg oral tablets administered twice daily (BID) for the full 24 months (including the randomized period Month 12 to Month 18) Receives: Drug: Simufilam 100 mg oral tablet |
| Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets | Placebo comparator | 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. Receives: Drug: Simufilam 100 mg oral tablet; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in ADAS-Cog-11
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.
Measured: Day 1 to Month 24
Change From Baseline in ADAS-Cog-11 (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.
Measured: Month 12 to Month 24
Safety and Tolerability (Open Label Abnormal Vital Signs)
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)
Measured: Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Vital Signs)
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
Measured: Month 12 to month 18
Safety and Tolerability (Open Label Electrocardiogram Results)
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)
Measured: Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Electrocardiogram Results)
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
Measured: Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Physical Examination)
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)
Measured: Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Physical Examination Findings)
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
Measured: Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Clinical Laboratory Results)
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)
Measured: Day 1 to Month 12 and month 18 to month 24
Safety and Tolerability (Randomize Withdraw Abnormal Clinical Laboratory Results)
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
Measured: Month 12 to Month 18
Secondary outcomes (5)
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Mean Concentration (pg/mL)
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)
Measured: Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Tau Protein Mean Concentration (pg/mL)
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)
Measured: Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurogranin Mean Concentration (pg/mL)
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)
Measured: Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurofilament Light Chain Protein Mean Concentration (pg/mL)
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)
Measured: Day 1 to Month 12
Change From Baseline to Month 12 in Cerebral Spinal Fluid for Glial Fibrillary Acidic Protein Mean Concentration (pg/mL)
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)
Measured: Day 1 to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start24 Mar 2020
- Primary completion9 Nov 2023
- Study completion9 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Approximately two hundred (200) patients will be enrolled into the study. All participants will receive open-label simufilam 100 mg b.i.d. for a year. At Month12, participants will be randomized (1:1) to continue taking simufilam 100 mg b.i.d. or to be switched to placebo for 6 months. At Month 18, all participants will enter a final 6-month treatment period of open-label simufilam 100 mg b.i.d.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cassava Sciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Lindsay Burns, PhD, Study chair, Cassava Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388254
- Sponsor's protocol ID
- PTI-125-04
- Other IDs
- R44AG065152
- Acronym
- PTI-125
- Status last verified
- Dec 2023
- First submitted
- 11 May 2020
- Last updated
- 22 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang HY, Pei Z, Lee KC, Lopez-Brignoni E, Nikolov B, Crowley CA, Marsman MR, Barbier R, Friedmann N, Burns LH. PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients. J Prev Alzheimers Dis. 2020;7(4):256-264. doi: 10.14283/jpad.2020.6.
PubMed 32920628Wang HY, Lee KC, Pei Z, Khan A, Bakshi K, Burns LH. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31.
PubMed 28438486Wang HY, Bakshi K, Frankfurt M, Stucky A, Goberdhan M, Shah SM, Burns LH. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84. doi: 10.1523/JNEUROSCI.0354-12.2012.
PubMed 22815492Brodtmann A, Darby D, Oboudiyat C, Mahoney CJ, Le Heron C, Panegyres PK, Brew B. Assessing preparedness for Alzheimer disease-modifying therapies in Australasian health care systems. Med J Aust. 2023 Apr 3;218(6):247-249. doi: 10.5694/mja2.51880. Epub 2023 Mar 19. No abstract available.
PubMed 36934371
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04388254
- Acronym / sponsor ID
- PTI-125 / PTI-125-04
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Cassava Sciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 24 Mar 2020 (actual)
- Primary completion
- 9 Nov 2023 (actual)
- Study completion
- 9 Nov 2023 (actual)
- First posted
- 14 May 2020 (actual)
- Results
- Posted 22 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Approximately two hundred (200) patients will be enrolled into the study. All participants will receive open-label simufilam 100 mg b.i.d. for a year. At Month12, participants will be randomized (1:1) to continue taking simufilam 100 mg b.i.d. or to be switched to placebo for 6 months. At Month 18, all participants will enter a final 6-month treatment period of open-label simufilam 100 mg b.i.d.
| Arm | Type | Receives |
|---|---|---|
| Simufilam 100 mg oral tablets throughout | Experimental | Drug: Simufilam 100 mg oral tabletSimufilam 100 mg oral tablets administered twice daily (BID) for the full 24 months (including the randomized period Month 12 to Month 18) |
| Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets | Placebo comparator | Drug: Simufilam 100 mg oral tablet, Drug: PlaceboThis 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. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Informed consent form (ICF) signed by the subject or legally acceptable representative.
- Patient has a caregiver or legal representative responsible for administering the drug and recording the time.
- Ages ≥ 50 and ≤ 85 years
- 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.
- If female, postmenopausal for at least 1 year
Key exclusion criteria (42 listed)
- Anything that in the opinion of the Investigator would preclude participation in a 2-year study.
- BMI < 18.5
- Positive urine drug screen.
- Positive HIV, HCV or HbsAg screen.
- Suicidality on C-SSRS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simufilam 100 mg oral tabletAlso: PTI-125, SumifilamSimufilam 100 mg oral tablet for b.i.d. administration | Drug | Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets, Simufilam 100 mg oral tablets throughout |
| PlaceboMatching placebo oral tablets | Drug | Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets |
Primary outcome
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.
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.
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)
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
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)
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
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)
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
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)
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
5 secondary outcomes
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 Tau Protein 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)
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)
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)
Time frame: Day 1 to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32920628Wang HY, Pei Z, Lee KC, Lopez-Brignoni E, Nikolov B, Crowley CA, Marsman MR, Barbier R, Friedmann N, Burns LH. PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients. J Prev Alzheimers Dis. 2020;7(4):256-264. doi: 10.14283/jpad.2020.6.
- Background: PubMed 28438486Wang HY, Lee KC, Pei Z, Khan A, Bakshi K, Burns LH. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31.
- Background: PubMed 22815492Wang HY, Bakshi K, Frankfurt M, Stucky A, Goberdhan M, Shah SM, Burns LH. Reducing amyloid-related Alzheimer's disease pathogenesis by a small molecule targeting filamin A. J Neurosci. 2012 Jul 18;32(29):9773-84. doi: 10.1523/JNEUROSCI.0354-12.2012.
- Derived from this study: PubMed 36934371Brodtmann A, Darby D, Oboudiyat C, Mahoney CJ, Le Heron C, Panegyres PK, Brew B. Assessing preparedness for Alzheimer disease-modifying therapies in Australasian health care systems. Med J Aust. 2023 Apr 3;218(6):247-249. doi: 10.5694/mja2.51880. Epub 2023 Mar 19. No abstract available.
- Individual participant dataSharing planned: No
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Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsay Burns, PhD study chair
Cassava Sciences
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simufilam 100 mg oral tablet in people with Alzheimer Disease, run by Cassava Sciences, Inc. at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in ADAS-Cog-11 (time frame: Day 1 to Month 24). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04388254, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2025.