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

NCT04079803 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PTI-125-02R44AG060878
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 9

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in CSF Abeta42

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

  Screening to Day 28

• Change From Baseline in CSF Total Tau.

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

  Screening to Day 28

• Change From Baseline in CSF P-tau181

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

  Screening to Day 28

• Change From Baseline in CSF Neurogranin

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

  Screening to Day 28

• Change From Baseline in CSF Neurofilament Light Chain

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

  Screening to Day 28

• Change From Baseline in CSF YKL-40

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

  Screening to Day 28

Secondary Outcomes (3)

• Paired Associates Learning Test

  Day 1 to Day 28

• Spatial Working Memory Test

  Day 1 to Day 28

• CSF IL-6, sTREM2, HMGB1, Albumin, IgG

  Screening to Day 28

Other Outcomes (3)

• 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

  Day 1 to Day 28

• Plasma P-tau181

  Day 1 to Day 28

• Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker

  Day 1 to Day 28

Study Arms (3)

Placebo Cohort

PLACEBO COMPARATOR

Subjects administered placebo oral tablets twice daily (BID)

Drug: Placebo oral tablet

Simufilam (PTI-125) 100 mg tablets Cohort

EXPERIMENTAL

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

Drug: Simufilam 50 mg oral tablet

Simufilam (PTI-125) 50 mg tablets Cohort

EXPERIMENTAL

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

Drug: Simufilam 100 mg tablet

Interventions

Placebo oral tablet DRUG

Oral placebo tablet

Placebo Cohort

Simufilam 100 mg tablet DRUG

Simufilam 100 mg oral tablet

Also known as: PTI-125

Simufilam (PTI-125) 50 mg tablets Cohort

Simufilam 50 mg oral tablet DRUG

Simufilam 50 mg oral tablet

Also known as: PTI-125

Simufilam (PTI-125) 100 mg tablets Cohort

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cassava Sciences, Inc.: lead
• National Institute on Aging (NIA): collaborator

Study Sites (9)

Cognitive Clinical Trials

Gilbert, Arizona, 85296, United States

Location

Cognitive Clinical Trials

Surprise, Arizona, 85374, United States

Location

Optimus U

Miami, Florida, 33125, United States

Location

IMIC, Inc.

Palmetto Bay, Florida, 33157, United States

Location

Cognitive Clinical Trials

Bellevue, Nebraska, 68005, United States

Location

Cognitive Clinical Trials

Omaha, Nebraska, 68116, United States

Location

Advanced Memory Research Institute

Toms River, New Jersey, 08755, United States

Location

Centex Studies, Inc.

Houston, Texas, 77058, United States

Location

Centex Studies, Inc.

McAllen, Texas, 78504, United States

Location

Related Publications (1)

• 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.

  PMID: 33188449 DERIVED

Related Links

• Altered filamin A enables amyloid beta-induced tau hyperphosphorylation and neuroinflammation in Alzheimer's disease

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Simufilam; Tablets

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Nadav Friedmann, PhD, MD, Chief Medical Officer
• Organization: Cassava Sciences, Inc.

nfriedmann@cassavasciences.com

512-501-1900

Study Officials

• Lindsay Burns, PhD

  Cassava Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: September 6, 2019
• Study Start: September 9, 2019
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: September 29, 2021
• Results First Posted: June 1, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)