Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT04388254
Recruitment Status : Active, not recruiting
First Posted : May 14, 2020
Last Update Posted : September 29, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Cassava Sciences, Inc.

Brief 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. 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.

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

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Matching placebo for the 6-month randomized period (Month 12 to Month 18)
Primary Purpose: Treatment
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
Actual Study Start Date : March 24, 2020
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Safety and Tolerability [ Time Frame: Day 1 to Month 24 ]
    Safety and tolerability of simufilam (PTI-125) during the full study: Open-label period 1 (Day 1 to Month 12), the randomized withdrawal (Month 12 to Month 18), and open-label period 2 (Month 18 to Month 24)

  2. Change from baseline in CSF P-tau, Total Tau, Abeta42, neurofilament light chain, neurogranin, YKL-40, soluble TREM2 and HMGB1 during first 6 months of open-label period 1 [ Time Frame: Screening to Month 6 ]
    Change from baseline in cerebrospinal fluid biomarkers of AD pathology, neurodegeneration and neuroinflammation during first 6 months of open-label period 1 in a subset of 25 subjects

  3. Change from baseline in ADAS-Cog-11 during open-label period 1 [ Time Frame: Day 1 to Month 12 ]
    Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition during open-label period 1

  4. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11) [ Time Frame: Month 12 to Month 18 ]
    Change in cognition vs. placebo during randomized withdrawal period


Secondary Outcome Measures :
  1. Neuropsychiatric Inventory (NPI) [ Time Frame: Day 1 to Month 12 ]
    Change from baseline in behavioral symptoms during open-label period 1

  2. Neuropsychiatric Inventory (NPI) [ Time Frame: Month 12 to Month 18 ]
    Change in neuropsychiatric symptoms vs. placebo during randomized withdrawal period

  3. Change from baseline in CSF P-tau, Total Tau, Abeta42, neurofilament light chain, neurogranin, YKL-40, soluble TREM2 and HMGB1 during open-label period 1 [ Time Frame: Screening to Month 12 ]
    Change from baseline in cerebrospinal fluid biomarkers of AD pathology, neurodegeneration and neuroinflammation during open-label period 1 in a subset of 25 subjects

  4. Change from baseline in plasma P-tau181 during open-label period 1 [ Time Frame: Day 1 to Month 12 ]
    Change from baseline in plasma concentrations (pg/mL) of phospho-tau181 during open-label period 1

  5. Change in plasma P-tau181 during randomized withdrawal period [ Time Frame: Month 12 to Mont 18 ]
    Change in plasma concentrations (pg/mL) of phospho-tau181 vs. placebo during randomized withdrawal period

  6. Change from baseline in plasma SavaDx during open-label period 1 [ Time Frame: Day 1 to Month 12 ]
    Change from baseline in a proprietary plasma biomarker during open-label period 1

  7. Change in plasma SavaDx during randomized withdrawal period [ Time Frame: Month 12 to Month 18 ]
    Change in a proprietary plasma biomarker during the randomized withdrawal.



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.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT04388254


Locations
Layout table for location information
United States, Arizona
Cognitive Clinical Trials
Gilbert, Arizona, United States, 85296
Cognitive Clinical Trials
Surprise, Arizona, United States, 85374
United States, California
Sun Valley Research Center, Inc.
Imperial, California, United States, 92251
United States, Florida
Brain Matters Research
Delray Beach, Florida, United States, 33445
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, United States, 33912
Adaptive Clinical Research, Inc
Miami Lakes, Florida, United States, 33016
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, 68130
United States, New Jersey
Advanced Memory Research Institute
Toms River, New Jersey, United States, 08755
United States, Ohio
Neuro-Behavioral Clinical Research
North Canton, Ohio, United States, 44720
United States, Texas
Senior Adults Specialty Research
Austin, Texas, United States, 78757
Centex Studies, Inc.
Houston, Texas, United States, 77058
Centex Studies
McAllen, Texas, United States, 78504
Canada, Ontario
Ottawa Memory Clinic
Ottawa, Ontario, Canada, K1Z 1G3
Toronto Memory Program
Toronto, Ontario, Canada, M3B 2S7
Sponsors and Collaborators
Cassava Sciences, Inc.
National Institute on Aging (NIA)
Investigators
Layout table for investigator information
Study Chair: Lindsay Burns, PhD Cassava Sciences
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Cassava Sciences, Inc.
ClinicalTrials.gov Identifier: NCT04388254    
Other Study ID Numbers: PTI-125-04
R44AG065152 ( U.S. NIH Grant/Contract )
First Posted: May 14, 2020    Key Record Dates
Last Update Posted: September 29, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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