CompletedPhase 2Results posted

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

A Phase 2a, Open-label, Multiple Dose, Safety, Pharmacokinetic and Biomarker Study of PTl-125 in Mild-to-moderate Alzheimer's Disease Patients

Lead sponsor

Pain Therapeutics

Asset

Simufilam

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 16-24•Study partner/caregiver required•Background AD symptomatic therapy, if used: stable ≥3 months

Primary endpoints

•Cmax•Cmax (Tmax)•Last Quantifiable Plasma Concentration (Clast)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03748706

Org study IDPTI-125-03

NihR44AG060878

Timeline

Milestones

Study first posted2018-11-21actual

Study start2019-03-07actual

Primary completion2019-05-08actual

Study completion2019-05-08actual

Results first posted2021-04-01actual

Last update posted2021-07-07actual

Assets

Drug assets

Simufilam

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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 <= 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

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

•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.

•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 CNS 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 or greater quaque die currently or within 3 months prior to enrollment in the study

•Discontinued AChEI < 30 days prior to enrollment in the study

•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 enrollment in the study

•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 enrollment in the study

•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 enrollment in the study

•Peripherally acting drugs with effects on cholinergic transmission

•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

•Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study

•Metformin or cimetidine.

Endpoints (16)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Amyloid biomarkers

Other (unclassified)

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

CSF Biomarkers

Time frame:Change from Baseline to Day 28

descriptive

Secondary/registry result

CSF Biomarkers

Time frame:Change from Baseline to Day 28

descriptive

Posted result

Group	Value (mean), % change from baseline	Standard deviation
PTI-125Total taun=13 Participants	-19.8	0.04
Abeta42n=13 Participants	4.3	0.05
p-tau181n=13 Participants	-34.4	0.05
Neurograninn=13 Participants	-32	0.02
Neurofilament light chainn=13 Participants	-22	0.02
YKL-40n=13 Participants	-9	0.01
IL-6n=13 Participants	-14	0.01
IL-1 betan=13 Participants	-11	0.01
TNF alphan=13 Participants	-5	0.01