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CompletedNCT04079803Updated Sep 29, 2021Results posted

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

A Phase 2 interventional study of Placebo oral tablet and Simufilam 100 mg tablet in Alzheimer Disease, sponsored by Cassava Sciences, Inc.. Completed at 9 sites in United States. Open to participants aged 50 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-09-29.

Sponsored by Cassava Sciences, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
64
Allocation
Randomized
Ages
50 Years to 85 Years
Sex
All
01

Study summary

This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients.

Read the detailed description

This is a Phase 2b, Randomized, Double-blind, Placebo-controlled, multiple dose study of PTI-125 in mild-to-moderate Alzheimer's disease patients. A total of sixty (60) patients will be enrolled in the study. Patients will receive Placebo, 50 mg or 100 mg b.i.d. of PTI-125. The objective of this study are to investigate the safety, and biomarkers of PTI-125 following 28-day repeat oral administration.

02

Conditions studied

  • Alzheimer Disease

Browse trials for

03

In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 64 is close to the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Cassava Sciences, Inc. is the lead sponsor of 9 studies on the registry; none are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 7 (78%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
64 participants (actual)

Study arms

  • Placebo comparator
    Placebo Cohort

    Subjects administered placebo oral tablets twice daily (BID)

    Drug: Placebo oral tablet

  • Experimental
    Simufilam (PTI-125) 100 mg tablets Cohort

    Subjects administered simufilam (PTI-125) 100 mg oral tablets twice daily (BID)

    Drug: Simufilam 50 mg oral tablet

  • Experimental
    Simufilam (PTI-125) 50 mg tablets Cohort

    Subjects administered simufilam (PTI-125) 50 mg oral tablets twice daily (BID)

    Drug: Simufilam 100 mg tablet

Interventions

  • DrugPlacebo oral tablet

    Oral placebo tablet

  • DrugSimufilam 100 mg tablet

    Simufilam 100 mg oral tablet

    Also known as: PTI-125

  • DrugSimufilam 50 mg oral tablet

    Simufilam 50 mg oral tablet

    Also known as: PTI-125

06

What researchers measure

Primary outcomes

  1. Change From Baseline in CSF Abeta42

    Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

    Time frame: Screening to Day 28

  2. Change From Baseline in CSF Total Tau.

    Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.

    Time frame: Screening to Day 28

  3. Change From Baseline in CSF P-tau181

    Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

    Time frame: Screening to Day 28

  4. Change From Baseline in CSF Neurogranin

    Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin

    Time frame: Screening to Day 28

  5. Change From Baseline in CSF Neurofilament Light Chain

    Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain

    Time frame: Screening to Day 28

  6. Change From Baseline in CSF YKL-40

    Change from Baseline (screening) in cerebrospinal fluid YKL-40

    Time frame: Screening to Day 28

Secondary outcomes

  1. Paired Associates Learning Test

    Cognitive test assessing episodic memory. Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.

    Time frame: Day 1 to Day 28

  2. Spatial Working Memory Test

    Cognitive assessment of spatial working memory: A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies.

    Time frame: Day 1 to Day 28

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

    Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity

    Time frame: Screening to Day 28

Other outcomes

  1. 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

    FLNA linkages to these two receptors were assessed by densitometric quantitation of immunoblot bands of each receptor (detected by a specific antibody) in anti-FLNA precipitates. The measure is noted as a ratio to total FLNA.

    Time frame: Day 1 to Day 28

  2. Plasma P-tau181

    Percent change in plasma P-tau181

    Time frame: Day 1 to Day 28

  3. Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker

    SavaDx is a novel plasma biomarker

    Time frame: Day 1 to Day 28

07

Results

Posted Jun 1, 2021

Participant flow

Participant flow — Overall Study
MilestonePlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Started222121
Completed222120
Not completed001
Withdrew: Withdrawal by subject001

Outcome measures

PrimaryChange From Baseline in CSF Abeta42

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF Abeta42
pg/mLPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Change From Baseline in CSF Abeta424.8 ± 30.912.5 ± 11.916.2 ± 21.1
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.087 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.01 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
PrimaryChange From Baseline in CSF Total Tau.

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF Total Tau.
pg/mLPlacebo CohortSimufilam (PTI-125) 100 mg Tablets CohortSimufilam (PTI-125) 50 mg Tablets Cohort
Change From Baseline in CSF Total Tau.-3.2 ± 14.8-18.7 ± 10.4-14.6 ± 9.6
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125) 100 mg Tablets Cohort · ANCOVA · p = <0.0001 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125) 50 mg Tablets Cohort · ANCOVA · p = 0.0012 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
PrimaryChange From Baseline in CSF P-tau181

Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF P-tau181
pg/mLPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Change From Baseline in CSF P-tau181-0.63 ± 1.8-3.1 ± 1.7-2.4 ± 1.6
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.005 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.002 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
PrimaryChange From Baseline in CSF Neurogranin

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF Neurogranin
pg/mLPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Change From Baseline in CSF Neurogranin-50.5 ± 434-648 ± 491-527 ± 361
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0002 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.0005 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
PrimaryChange From Baseline in CSF Neurofilament Light Chain

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF Neurofilament Light Chain
pg/mLPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Change From Baseline in CSF Neurofilament Light Chain-10.0 ± 45-76.3 ± 50.6-49.7 ± 35.5
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0003 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.0058 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
PrimaryChange From Baseline in CSF YKL-40

Change from Baseline (screening) in cerebrospinal fluid YKL-40

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL
Change From Baseline in CSF YKL-40
pg/mLPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Change From Baseline in CSF YKL-40-0.96 ± 24.2-22.3 ± 11.7-20.4 ± 17.4
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0001 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.0001 (P value adjusted for multiplicity of 6 co-primary endpoints (p\<0.008 required for significance).)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
SecondaryPaired Associates Learning Test

Cognitive test assessing episodic memory. Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.

Time frame:
Day 1 to Day 28
Reported as:
Mean · Change from Day 1 in total errors
Paired Associates Learning Test
Change from Day 1 in total errorsPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Paired Associates Learning Test-1.5 ± 8.5-4.5 ± 17.7-5.7 ± 13.6
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · Effect size: 0.23Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · Effect size: 0.37Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.
SecondarySpatial Working Memory Test

Cognitive assessment of spatial working memory: A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies.

Time frame:
Day 1 to Day 28
Reported as:
Mean · Change from Day 1 in total errors
Spatial Working Memory Test
Change from Day 1 in total errorsPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Spatial Working Memory Test-0.41 ± 7.54-2.31 ± 7.45-3.35 ± 4.86
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · Effect size: 0.46Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was almost identical (0.45) when calculated by Cohen's d.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · Effect size: 0.25Reported effect size vs. placebo was calculated with Hedge's g (for groups of 20 or fewer) but was identical when calculated by Cohen's d.
SecondaryCSF IL-6, sTREM2, HMGB1, Albumin, IgG

Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity

Time frame:
Screening to Day 28
Reported as:
Mean · pg/mL; optical density for albumin & IgG
CSF IL-6, sTREM2, HMGB1, Albumin, IgG
pg/mL; optical density for albumin & IgGPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
CSF IL-6-1.1 ± 2.0-3.7 ± 1.8-3.3 ± 1.9
CSF sTREM2-77.3 ± 510-426 ± 274-424 ± 386
CSF HMGB119.4 ± 172.3-143 ± 51.3-152 ± 50.1
CSF albumin-240 ± 1620-2292 ± 1760-1245 ± 1735
CSF IgG-574.8 ± 2518-2350 ± 2517-2444 ± 2097
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0078 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.019 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0002 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.0007 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0001 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.0001 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.0001 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.046 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANCOVA · p = 0.012 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANCOVA · p = 0.014 (Secondary CSF biomarkers were not adjusted for multiplicity.)General Linear Model for the analysis of covariance (ANCOVA) with a two-sided 95% confidence interval and baseline measurement as the covariate.
Other pre-specifiedTarget 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

FLNA linkages to these two receptors were assessed by densitometric quantitation of immunoblot bands of each receptor (detected by a specific antibody) in anti-FLNA precipitates. The measure is noted as a ratio to total FLNA.

Time frame:
Day 1 to Day 28
Reported as:
Mean · ratio to total FLNA
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
ratio to total FLNAPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
FLNA - alpha7nAChR linkage-0.07 ± 0.19-0.24 ± 0.16-0.23 ± 0.13
FLNA - TLR4 linkage-0.05 ± 0.18-0.19 ± 0.14-0.19 ± 0.11
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANOVA · p = 0.005 (As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.)ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANOVA · p = 0.009 (As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.)ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value.
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANOVA · p = 0.01 (As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.)ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value.
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANOVA · p = 0.01 (As secondary endpoints, lymphocyte biomarkers were not adjusted for multiplicity.)ANOVA was used instead of ANCOVA due to the range in baseline values; it was deemed more appropriate to compare to each subject's own baseline value.
Other pre-specifiedPlasma P-tau181

Percent change in plasma P-tau181

Time frame:
Day 1 to Day 28
Reported as:
Mean · Percent change
Plasma P-tau181
Percent changePlacebo CohortSimufilam (PTI-125) 100 mg Tablets CohortSimufilam (PTI-125) 50 mg Tablets Cohort
Plasma P-tau18120.7 ± 49-16.5 ± 29-15.1 ± 36
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125) 100 mg Tablets Cohort · ANOVA · p = 0.01ANOVA followed by Dunnett's multiple comparisons test.
  • Placebo Cohort vs Simufilam (PTI-125) 50 mg Tablets Cohort · ANOVA · p = 0.02ANOVA followed by Dunnett's multiple comparisons test.
  • Placebo Cohort vs Simufilam (PTI-125) 100 mg Tablets Cohort vs Simufilam (PTI-125) 50 mg Tablets Cohort · ANOVA · p = 0.009This p value is for the main effect of treatment of the ANOVA.
Other pre-specifiedPercent Change From Baseline in SavaDx, a Novel Plasma Biomarker

SavaDx is a novel plasma biomarker

Time frame:
Day 1 to Day 28
Reported as:
Mean · Percent change
Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker
Percent changePlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker-3.2 ± 62-47.8 ± 19-44.1 ± 35
Statistical analysis
  • Placebo Cohort vs Simufilam (PTI-125), 100 mg Tablets Cohort · ANOVA · p = 0.003
  • Placebo Cohort vs Simufilam (PTI-125), 50 mg Tablets Cohort · ANOVA · p = 0.016

Adverse events

Collected over 28 days. Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo Cohort0/22 (0%)0/22 (0%)12/22 (54.5%)
Simufilam (PTI-125), 100 mg Tablets Cohort0/21 (0%)0/21 (0%)9/21 (42.9%)
Simufilam (PTI-125), 50 mg Tablets Cohort0/21 (0%)0/21 (0%)4/21 (19%)
Most frequent other events
Most frequent other events
EventPlacebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets Cohort
Any adverse eventGeneral disorders12/229/214/21
HeadacheNervous system disorders3/222/211/21
FatigueMetabolism and nutrition disorders2/220/211/21
NauseaGastrointestinal disorders2/221/210/21

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
<=18 years0000
Between 18 and 65 years49619
>=65 years18121545
Age, Continuous
Age, Continuous(years)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Mean71.3 ± 6.6869.3 ± 5.4767.1 ± 8.7669.2 ± 6.97
Sex: Female, Male
Sex: Female, Male(Participants)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Female11121235
Male119929
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Hispanic or Latino9111131
Not Hispanic or Latino13101033
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
American Indian or Alaska Native0000
Asian1001
Native Hawaiian or Other Pacific Islander0000
Black or African American2248
White19191755
More than one race0000
Unknown or Not Reported0000
CSF total tau/Aβ42 ratio
CSF total tau/Aβ42 ratio(ratio)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Mean1.20 ± 0.551.08 ± 0.501.17 ± 0.581.15 ± 0.54
Mini-Mental State Exam (MMSE)
Mini-Mental State Exam (MMSE)(units on a scale)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Mean23.1 ± 2.7823.0 ± 2.6622.7 ± 2.6722.9 ± 2.70
Taking cholinesterase inhibitor or memantine
Taking cholinesterase inhibitor or memantine(Participants)Placebo CohortSimufilam (PTI-125), 100 mg Tablets CohortSimufilam (PTI-125), 50 mg Tablets CohortTotal
Count of participants87520

17 further baseline measures are reported on the registry.

08

Study locations

9 sites
  • Cognitive Clinical Trials
    Gilbert, Arizona 85296, United States
  • Cognitive Clinical Trials
    Surprise, Arizona 85374, United States
  • Optimus U
    Miami, Florida 33125, United States
  • IMIC, Inc.
    Palmetto Bay, Florida 33157, United States
  • Cognitive Clinical Trials
    Bellevue, Nebraska 68005, United States
  • Cognitive Clinical Trials
    Omaha, Nebraska 68116, United States
  • Advanced Memory Research Institute
    Toms River, New Jersey 08755, United States
  • Centex Studies, Inc.
    Houston, Texas 77058, United States
  • Centex Studies, Inc.
    McAllen, Texas 78504, United States
09

References and documents

Publications

  • Sever S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol. 2021 Sep;36(9):2607-2614. doi: 10.1007/s00467-020-04812-z. Epub 2020 Nov 13. PubMed 33188449 ↗

Study documents

  • Study protocol · Jun 28, 2019
  • Statistical analysis plan · Feb 12, 2020
  • Informed consent form · Jul 10, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 29, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04079803
Lead sponsor
Cassava Sciences, Inc.
Collaborators
National Institute on Aging (NIA)
Responsible party
Sponsor
First posted
Sep 6, 2019
Start date
Sep 9, 2019
Primary completion
Mar 31, 2020
Completion
Mar 31, 2020
Results posted
Jun 1, 2021
Last update
Sep 29, 2021

Study contacts

Lindsay Burns, PhD
study director · Cassava Sciences, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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Discussion

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