[18F]PI-2620 Phase 3 Histopathological Study

Official title

An Open-label, Non-randomized, Multi-center Pivotal Phase 3 Study to Evaluate the Efficacy and Safety of PET Imaging With [18F]PI-2620 for the Detection of Tau Deposition When Compared to Post-mortem Histopathology (ADvance)

Overview

This study is an open-label, multi-center, non-randomized pivotal Phase 3 study to assess the efficacy and safety of PET imaging with \[18F\]PI-2620 for detection of tau deposition in subjects with Alzheimer's disease (AD) and controls during lifetime when compared to histopathology obtained after death and completion of brain autopsy.

Interventions

• Drug [18F]PI-2620
  The radioligand, \[18F\]PI-2620, will be injected intravenously at a dose of 185 MBq ± 20%

Primary outcome measures

• Diagnostic Efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating tau neurofibrillary pathology associated with AD (NFT Score of B0 or B1 = negative) [Time frame: At autopsy, until study completion with an average of 1 year]

Secondary outcome measures (4)

• Diagnostic Efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating tau neurofibrillary pathology associated with AD (NFT Score of B0, B1 or B2 = negative) [Time frame: At autopsy, until study completion with an average of 1 year]
• Diagnostic efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating levels of AD neuropathologic change (ADNC) ('No' or 'Low' levels of ADNC = negative) [Time frame: At autopsy, until study completion with an average of 1 year]
• Diagnostic efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating levels of ADNC ('No', 'Low' or 'Intermediate" levels of ADNC = negative) [Time frame: At autopsy, until study completion with an average of 1 year]
• Inter-reader agreement for the visual assessment of [18F]PI-2620 PET images [Time frame: Baseline scan]

Eligibility criteria

Inclusion criteria

Only subjects who meet all of the following criteria will be eligible for enrollment into the study:

• Males and females aged 50 years and over
• Have a projected life expectancy of ≤ 1 year as determined by the investigator (terminal medical condition including but not limited to end-stage dementia, end-stage congestive heart failure, end-stage chronic obstructive pulmonary disease (COPD), or end-stage cancer)
• Written informed consent obtained from the subject and/or the subject's legally authorized representative (LAR), as applicable, to consent for study procedures and brain donation (consent consistent with the legal requirements of the State in which the subject dies)
• Can tolerate study procedures including lying down in PET scanner. The investigator will carefully assess each subject and use medical judgment to determine whether the subject can tolerate the imaging procedure

Exclusion criteria

Subjects will be excluded from the enrollment if they:

• Are receiving aggressive treatment with life sustaining measures (e.g. receiving chemotherapy; palliative chemotherapy is allowed)
• Are known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment (e.g. lesions are typically > 2 cm at their greatest extent and may include stroke, primary or metastatic neoplasm, other tumors or cystic lesions. Subjects with a history of major stroke or traumatic brain injury or other structural lesion as well as cases with a history of primary Central Nervous System (CNS) neoplasm or known metastatic cancer must be discussed with the study sponsor prior to enrollment)
• Have suspected encephalopathy due to alcoholism or end-stage liver disease
• Are known to have a Glomerular Filtration Rate below < 15 mL/min
• Have received an investigational or approved therapy directly targeting amyloid or tau
• Are females of childbearing potential who are pregnant, lactating or breastfeeding, or who are not using adequate contraception
• Have implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI (in case an MRI is planned to be performed)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 25 centers

• Barrow Neurological Institute — Phoenix
• Banner Sun Health Research Institute — Sun City
• UC Los Angeles — Los Angeles
• Esperanza Clinical — Murrieta
• Sutter Health — San Francisco
• Galiz Research — Hialeah
• UF College of Medicine - Jacksonville — Jacksonville
• K2 Medical Research — Lady Lake
• … and 17 more centers

Identifiers

NCT: NCT05641688 · LMT-01-01-22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗