Study Stopped
Samus Therapeutics company closure
To Evaluate Safety, Tolerability and Pharmacological Effects of PU AD in Subjects With Mild AD Dementia
A Phase 2A Study to Evaluate Safety, Tolerability and Pharmacological Effects of PU AD in Subjects With Mild Alzheimer's Disease (AD) Dementia
1 other identifier
interventional
4
1 country
10
Brief Summary
The study is designed as a classic, randomized, double blind, placebo controlled, parallel group study including one active dose of PU AD and matching placebo, designed to assess safety, tolerability and pharmacological effects of oral PU AD (dihydrochloride salt) in subjects with mild AD
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 alzheimer-disease
Started Jun 2020
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 12, 2020
CompletedFirst Posted
Study publicly available on registry
March 17, 2020
CompletedStudy Start
First participant enrolled
June 30, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 9, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 15, 2022
CompletedNovember 17, 2022
November 1, 2022
2 months
March 12, 2020
November 14, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
Fluorodeoxyglucose Positron emission tomography (FDG-PET)
Change from baseline in pharmacologic parameters over 6 months for FDG-PET measurements
6 months
incidence and severity of Adverse Events (AEs), serious adverse events (SAEs)
safety and tolerability, assessed by incidence and severity of AEs, SAEs, and AE's leading to withdrawal of treatment during the course of the study
6 months
Secondary Outcomes (5)
Tau Positron emission tomography (Tau PET )standardized uptake value ratio (SUVR)
6 months
Ratio of p-Tau to t-tau in Cerebrospinal fluid (CSF)
6 months
Alzheimer's Disease composite score (ADCOMS)
6 months
Global Statistical Test (GST) combining Alzheimer's Disease Assessment Scale Cognitive (ADAS-Cog), Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and Clinical Dementia Rating Sum of Boxes (CDR-sb)
6 months
Pharmacokinetic (PK)
6 months
Study Arms (2)
30 mg PU AD
ACTIVE COMPARATOR75 subjects will be treated with active PU-AD on a 1:1 ratio qd
30 mg Placebo
PLACEBO COMPARATOR75 subjects will be treated with placebo SyrSpend on a 1:1 ratio qd
Interventions
Tau PET imaging enables the longitudinal assessment of the spatial pattern of tau deposition. Tau accumulates with progression of AD dementia and may be sensitive to disease related changes, particularly those due to intervention with a drug thought to work through a tau related mechanism. Quantitative assessments will be utilized to evaluate the target engagement and pharmacological effects of PU-AD after 6 months of treatment
Measurement of neuronal function with FDG PET can help to understand the relationship between target engagement and potential clinical effects. FDG PET will be acquired using stringent quality control. Since glucose metabolism captures all neuronal activity, in order to isolate effects due to treatment, patients will be maintained in a consistent state during the tracer uptake period. Subject motion during image acquisition will be minimized and monitored. Images will be quality controlled, processed, and measured quantitatively using methods that maximize signal to noise associated with technical and physiologic variability
A broad set of biomarkers are being assessed in this study to indicate whether this treatment is able to impact multiple pathways associated with AD related to neurodegeneration
Changes in blood biomarkers may be observable if treatment affects cerebral amyloidosis and loss of nerve cells
Alzheimer's Disease composite score (ADCOMS+), CDR sb, Alzheimer's Disease Assessment Scale Cognitive (ADAS cog), Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS ADL), Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale Cognitive (ADAS-COG 12)
Eligibility Criteria
You may qualify if:
- Male or female aged 55 to 80 years old (inclusive)
- Diagnosis of probable AD dementia based on National Institute on Aging and Alzheimer's Association (NIA/AA) AD Dementia diagnostic criteria
- Mild AD as assessed by Mini Mental State Examination (MMSE) score between 18 to 26 at Screening Visit (inclusive)
- Tau positive as evaluated by Tau PET using 18F-PI-2620 and assessment of tracer uptake in the medial temporal lobe and any cortical regions associated with Alzheimer's disease.
- Geriatric Depression Scale score of ≤ 6 (on the staff administered short form)
- Magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD
- Subjects or his/her caregiver and/or legally authorized representative must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent Form (ICF)
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
- Must have one caregiver who, in the investigator's judgment, has frequent and sufficient contact with the subject (at least 10 hours/week) and is able to provide accurate information about the subject's cognitive and functional abilities; the caregiver must agree to, accompany the subject to clinic visits and/or be available by phone at designated times to provide information to the investigator and study staff about the subject, attend in person clinic visits that require partner input for scale completion, and must agree to monitor the subject's administration of any prescribed medications
- Female must either be post menopausal (no menstrual period for \>1 year), or surgically sterilized (by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).
- Males who are sexually active and whose partners are females of childbearing potential must agree to use condoms from screening through 90 days after administration of the last dose of IMP; their partners must be willing to use a medically acceptable method of contraception (a barrier method, intrauterine device, or hormonal contraception) from screening through 90 days after administration of the last dose of IMP
- Must consent to Apolipoprotein E (ApoE) genotyping; the subject's ApoE status may be disclosed to him/her at the investigator's discretion -
You may not qualify if:
- Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
- Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and pharmacologic effect in this study; or has a life expectancy of \< 2 years
- Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
- Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate specific antigen post treatment
- Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe post treatment hypersensitivity reactions
- Has a "yes" answer to Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior assessment within 6 months of Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening
- Has received acetylcholinesterase inhibitor (AChEIs), memantine, and/or other AD therapy for less than 4 months or has less than 2 months of stable therapy on these treatments
- Has not been stable on medications that affect the Central nervous system (CNS), for at least 4 weeks (including antidepressants, hypnotics, antipsychotics, etc.) except occasional use of benzodiazepine (definition of occasional use - not more than twice in a week or three times in a month during the past 3 months).
- Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
- Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the investigator, might be a contributing cause to the subject's cognitive impairment (e.g., current history of substance abuse, uncontrolled vitamin B12 deficiency or abnormal thyroid function, stroke or other cerebrovascular condition, Parkinson's disease, Lewy body dementia, or frontotemporal dementia)
- Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening Visit
- History of bleeding disorder or predisposing conditions, blood clotting, or clinically significant abnormal results on coagulation profile at Screening, as determined by the investigator
- History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening Visit
- Clinically significant 12 lead Electrocardiogram (ECG) abnormalities, as determined by the investigator
- Indication of impaired liver function as shown by an abnormal liver function profile at Screening (e.g., repeated values of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≥ 2 × the upper limit of normal \[ULN\]) and/or indication of impaired renal function at Screening (e.g., repeated values of creatinine and blood urea nitrogen \[BUN\] ≥ 1.5 × Upper limit of normal (ULN) or estimated glomerular filtration rate \< 45 mL/minute/1.73 m2 and corroborating medical history and physical examination)
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
SFM Clinical Research, LLC
Boca Raton, Florida, 33487, United States
Brain Matters Research
Delray Beach, Florida, 33445, United States
JEM Research
Lake Worth, Florida, 33462, United States
Med-Care Research
Miami, Florida, 33165, United States
Miami Dade Medical Research Institute, LLC
Miami, Florida, 33173, United States
Neurostudies, Inc
Port Charlotte, Florida, 33952, United States
Premiere Research Institute
West Palm Beach, Florida, 33407, United States
Conquest Research LLC
Winter Park, Florida, 32789, United States
Advanced Clinical Institute, Inc.
Neptune City, New Jersey, 07753, United States
Princeton Medical Institute
Princeton, New Jersey, 08540, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Michael H Silverman, MD
Samus Therapeutics Consultant
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- All subjects, investigators, and study site personnel will be blinded to dose assignment. The Data Safety Monitoring Board (DSMB) will have access to unblinded safety data and will conduct review of these data at regular intervals during the study
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 12, 2020
First Posted
March 17, 2020
Study Start
June 30, 2020
Primary Completion
September 9, 2020
Study Completion
November 15, 2022
Last Updated
November 17, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share