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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04079803
Recruitment Status : Completed
First Posted : September 6, 2019
Results First Posted : June 1, 2021
Last Update Posted : September 29, 2021
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Cassava Sciences, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Placebo oral tablet Drug: Simufilam 100 mg tablet Drug: Simufilam 50 mg oral tablet Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Approximately sixty (60) patients will be enrolled into the study and randomized to one of three cohorts. Cohorts will receive placebo or PTI-125 at 50 or 100 mg b.i.d. (n=20 per group)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The sponsor, participant, care provider, investigator including sub-investigators and outcomes assessors will be blinded to throughout the study which includes using an Integrated Web Response System (IWRS) and electronic data capture (EDC) to ensure blinding during the study.
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multiple Dose, Biomarker and Safety Study of PTI-125 in Mild-to-moderate Alzheimer's Disease Patients
Actual Study Start Date : September 9, 2019
Actual Primary Completion Date : March 31, 2020
Actual Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo Cohort
Subjects administered placebo oral tablets twice daily (BID)
Drug: Placebo oral tablet
Oral placebo 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
Simufilam 50 mg oral tablet
Other Name: PTI-125

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
Simufilam 100 mg oral tablet
Other Name: PTI-125

Primary Outcome Measures :
  1. Change From Baseline in CSF Abeta42 [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

  2. Change From Baseline in CSF Total Tau. [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.

  3. Change From Baseline in CSF P-tau181 [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

  4. Change From Baseline in CSF Neurogranin [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin

  5. Change From Baseline in CSF Neurofilament Light Chain [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain

  6. Change From Baseline in CSF YKL-40 [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening) in cerebrospinal fluid YKL-40

Secondary Outcome Measures :
  1. Paired Associates Learning Test [ Time Frame: Day 1 to Day 28 ]
    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.

  2. Spatial Working Memory Test [ Time Frame: Day 1 to Day 28 ]
    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.

  3. CSF IL-6, sTREM2, HMGB1, Albumin, IgG [ Time Frame: Screening to Day 28 ]
    Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity

Other Outcome Measures:
  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 [ Time Frame: Day 1 to Day 28 ]
    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.

  2. Plasma P-tau181 [ Time Frame: Day 1 to Day 28 ]
    Percent change in plasma P-tau181

  3. Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker [ Time Frame: Day 1 to Day 28 ]
    SavaDx is a novel plasma biomarker

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04079803

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United States, Arizona
Cognitive Clinical Trials
Gilbert, Arizona, United States, 85296
Cognitive Clinical Trials
Surprise, Arizona, United States, 85374
United States, Florida
Optimus U
Miami, Florida, United States, 33125
IMIC, Inc.
Palmetto Bay, Florida, United States, 33157
United States, Nebraska
Cognitive Clinical Trials
Bellevue, Nebraska, United States, 68005
Cognitive Clinical Trials
Omaha, Nebraska, United States, 68116
United States, New Jersey
Advanced Memory Research Institute
Toms River, New Jersey, United States, 08755
United States, Texas
Centex Studies, Inc.
Houston, Texas, United States, 77058
Centex Studies, Inc.
McAllen, Texas, United States, 78504
Sponsors and Collaborators
Cassava Sciences, Inc.
National Institute on Aging (NIA)
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Study Director: Lindsay Burns, PhD Cassava Sciences, Inc.
  Study Documents (Full-Text)

Documents provided by Cassava Sciences, Inc.:
Study Protocol  [PDF] June 28, 2019
Statistical Analysis Plan  [PDF] February 12, 2020
Informed Consent Form  [PDF] July 10, 2019

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Cassava Sciences, Inc. Identifier: NCT04079803    
Other Study ID Numbers: PTI-125-02
R44AG060878 ( U.S. NIH Grant/Contract )
First Posted: September 6, 2019    Key Record Dates
Results First Posted: June 1, 2021
Last Update Posted: September 29, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders