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

NCT03748706 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PTI-125-03R44AG060878
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax)

  Blood draws will be done to evaluate levels of PTI-125 in the plasma using non-compartmental methods in WinNonlin.

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

• Time to Maximum Plasma Concentration (Tmax)

  Levels of PTI-125 will be assessed to determine how long it takes to reach the Cmax

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

• Last Quantifiable Plasma Concentration (Clast)

  Levels of PTI-125 will be assessed to determine the last time point where PTI-125 can be detected.

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

• Time to Last Quantifiable Plasma Concentration (Tlast)

  Levels of PTI-125 will be assessed to determine the elapsed time to where PTI-125 can last be detected in the plasma.

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

• Area Under the Curve (AUClast)

  AUC for PTI-125 plasma concentration from time zero to the last quantifiable plasma concentration.

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

• Plasma Half-life (T1/2)

  Assessment of the half-life in plasma of PTI-125

  Study Day 1 and Day 28 at 20, 40, and 60 min and at 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-dose

Secondary Outcomes (2)

• SavaDx (Biomarker)

  Study Day 1 and Day 28

• CSF Biomarkers

  Change from Baseline to Day 28

Study Arms (1)

Simufilam (PTI-125)

EXPERIMENTAL

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

Drug: PTI-125, 100 mg tablets

Interventions

PTI-125, 100 mg tablets DRUG

PTI-125, 100 mg tablets taken twice a day for 28 days

Simufilam (PTI-125)

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 \<= 24 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-hour) 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 (90 days) before screening and with continuous dosing for at least 3 months. If receiving donepezil, receiving any dose lower than 23 mg once daily.
• The patient is a non-smoker for at least 12 months.
• 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/Abeta42 in cerebrospinal fluid \>= 0.30.
• 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
• Residence in a skilled nursing facility
• 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 or requiring insulin
• Renal insufficiency (serum creatinine \>2.0 mg/dL)
• 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) \>2 times the upper limit of normal or total bilirubin greater than the upper limit of normal.
• 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 value \>= 450 msec for males or \>= 470 msec for females.

Sponsors & Collaborators

• Pain Therapeutics: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Insite Clinical Research

DeSoto, Texas, 75115, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Related Publications (3)

• Wang 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.

  PMID: 28438486 BACKGROUND

• Wang 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.

  PMID: 22815492 BACKGROUND

• 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.

  PMID: 32920628 RESULT

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Simufilam

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lindsay Burns, SVP of Neuroscience
• Organization: Cassava Sciences

lburns@cassavasciences.com

512-501-2484

Study Officials

• Lindsay Burns, PhD

  Cassava Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 21, 2018
• Study Start: March 7, 2019
• Primary Completion: May 8, 2019
• Study Completion: May 8, 2019
• Last Updated: July 7, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)