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

Phase 2

Completed

Conditions: Alzheimer Disease

Interventions: Drug: Simufilam 50 mg oral tablet
Drug: Placebo oral tablet
Drug: Simufilam 100 mg tablet

Registration Number: NCT04079803

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simufilam (PTI-125) 100 mg tablets Cohort	Simufilam 50 mg oral tablet	Subjects administered simufilam (PTI-125) 100 mg oral tablets twice daily (BID)
Placebo Cohort	Placebo oral tablet	Subjects administered placebo oral tablets twice daily (BID)
Simufilam (PTI-125) 50 mg tablets Cohort	Simufilam 100 mg tablet	Subjects administered simufilam (PTI-125) 50 mg oral tablets twice daily (BID)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in CSF Abeta42	Screening to Day 28	Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42
Change From Baseline in CSF Neurofilament Light Chain	Screening to Day 28	Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain
Change From Baseline in CSF Total Tau.	Screening to Day 28	Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.
Change From Baseline in CSF Neurogranin	Screening to Day 28	Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin
Change From Baseline in CSF YKL-40	Screening to Day 28	Change from Baseline (screening) in cerebrospinal fluid YKL-40
Change From Baseline in CSF P-tau181	Screening to Day 28	Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

Secondary Outcome Measures

Name	Time	Method
Paired Associates Learning Test	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.
Spatial Working Memory Test	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.
CSF IL-6, sTREM2, HMGB1, Albumin, IgG	Screening to Day 28	Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity

Trial Locations

Locations (5): Cognitive Clinical Trials
🇺🇸
Omaha, Nebraska, United States
Advanced Memory Research Institute
🇺🇸
Toms River, New Jersey, United States
Optimus U
🇺🇸
Miami, Florida, United States
IMIC, Inc.
🇺🇸
Palmetto Bay, Florida, United States
Centex Studies, Inc.
🇺🇸
McAllen, Texas, United States