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

NCT ID: NCT04079803

Last Updated: 2021-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-09
• Study Completion Date: 2020-03-31

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.

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Cohort

Subjects administered placebo oral tablets twice daily (BID)

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Oral placebo tablet

Simufilam (PTI-125) 100 mg tablets Cohort

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

Group Type: EXPERIMENTAL

Simufilam 50 mg oral tablet

Intervention Type: DRUG

Simufilam 50 mg oral tablet

Simufilam (PTI-125) 50 mg tablets Cohort

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

Group Type: EXPERIMENTAL

Simufilam 100 mg tablet

Intervention Type: DRUG

Simufilam 100 mg oral tablet

Interventions

Placebo oral tablet

Oral placebo tablet

Intervention Type: DRUG

Simufilam 100 mg tablet

Simufilam 100 mg oral tablet

Intervention Type: DRUG

Simufilam 50 mg oral tablet

Simufilam 50 mg oral tablet

Intervention Type: DRUG

Other Intervention Names

PTI-125; PTI-125

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Cassava Sciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lindsay Burns, PhD

Role: STUDY_DIRECTOR

Cassava Sciences, Inc.

Locations

Centex Studies, Inc.

McAllen, Texas, United States

Cognitive Clinical Trials

Gilbert, Arizona, United States

Cognitive Clinical Trials

Surprise, Arizona, United States

Optimus U

Miami, Florida, United States

IMIC, Inc.

Palmetto Bay, Florida, United States

Cognitive Clinical Trials

Bellevue, Nebraska, United States

Cognitive Clinical Trials

Omaha, Nebraska, United States

Advanced Memory Research Institute

Toms River, New Jersey, United States

Centex Studies, Inc.

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33188449 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://nnjournal.net/article/view/2313

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

Other Identifiers

R44AG060878

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PTI-125-02

Identifier Type: -

Identifier Source: org_study_id