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[18F]PI-2620 Phase 3 Histopathological Study

Primary Purpose

Alzheimer Disease

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
[18F]PI-2620
Sponsored by
Life Molecular Imaging Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer Disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Barrow Neurological InstituteRecruiting
  • Banner Sun Health Research InstituteRecruiting
  • Sutter Health
  • Galiz ResearchRecruiting
  • ClinCloud ResearchRecruiting
  • K2 Medical ResearchRecruiting
  • Verus Clinical ResearchRecruiting
  • Miami Jewish Health SystemsRecruiting
  • The Roskamp Institute
  • Charter ResearchRecruiting
  • Headlands Research
  • Velocity Clinical ResearchRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PI-2620 PET Scan

Arm Description

Outcomes

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)
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. NFT scores (as defined in Hyman et al. 2012) will be used as pathology assessment SoT (standard of truth). Tau neurofibrillary pathology associated with AD is defined as either negative with NFT Scores of B0 or B1 or positive NFT Scores of B2 or B3. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.

Secondary 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, B1 or B2 = negative)
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. NFT scores (as defined in Hyman et al. 2012) will be used as pathology assessment SoT (standard of truth). Tau neurofibrillary pathology associated with AD is defined as either negative with NFT Scores of B0, B1 or B2 or positive NFT Scores of B3. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
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)
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. ADNC levels according to NIA-AA criteria (Hyman et al., 2012) will be used as pathology assessment SoT (standard of truth). Level of ADNC according to NIA-AA criteria (considering Braak stage, Thal plaque score, and CERAD amyloid neuritic plaque score) is defined as either negative with 'no' or 'low' ADNC levels or positive with 'intermediate' or 'high' ADNC levels. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
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)
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. ADNC levels according to NIA-AA criteria (Hyman et al., 2012) will be used as pathology assessment SoT (standard of truth). Level of ADNC according to NIA-AA criteria (considering Braak stage, Thal plaque score, and CERAD amyloid neuritic plaque score) is defined as either negative with 'no', 'low' or 'intermediate' ADNC levels or positive with 'high' ADNC levels. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
Inter-reader agreement for the visual assessment of [18F]PI-2620 PET images
Fleiss kappa will be used to measure the inter-reader agreement for the visual assessment of [18F]PI-2620 PET images.

Full Information

First Posted
November 17, 2022
Last Updated
September 1, 2023
Sponsor
Life Molecular Imaging Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05641688
Brief Title
[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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Life Molecular Imaging Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PI-2620 PET Scan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
[18F]PI-2620
Intervention Description
The radioligand, [18F]PI-2620, will be injected intravenously at a dose of 185 MBq ± 20%
Primary Outcome Measure Information:
Title
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)
Description
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. NFT scores (as defined in Hyman et al. 2012) will be used as pathology assessment SoT (standard of truth). Tau neurofibrillary pathology associated with AD is defined as either negative with NFT Scores of B0 or B1 or positive NFT Scores of B2 or B3. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
Time Frame
At autopsy, until study completion with an average of 1 year
Secondary Outcome Measure Information:
Title
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)
Description
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. NFT scores (as defined in Hyman et al. 2012) will be used as pathology assessment SoT (standard of truth). Tau neurofibrillary pathology associated with AD is defined as either negative with NFT Scores of B0, B1 or B2 or positive NFT Scores of B3. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
Time Frame
At autopsy, until study completion with an average of 1 year
Title
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)
Description
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. ADNC levels according to NIA-AA criteria (Hyman et al., 2012) will be used as pathology assessment SoT (standard of truth). Level of ADNC according to NIA-AA criteria (considering Braak stage, Thal plaque score, and CERAD amyloid neuritic plaque score) is defined as either negative with 'no' or 'low' ADNC levels or positive with 'intermediate' or 'high' ADNC levels. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
Time Frame
At autopsy, until study completion with an average of 1 year
Title
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)
Description
[18F]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. ADNC levels according to NIA-AA criteria (Hyman et al., 2012) will be used as pathology assessment SoT (standard of truth). Level of ADNC according to NIA-AA criteria (considering Braak stage, Thal plaque score, and CERAD amyloid neuritic plaque score) is defined as either negative with 'no', 'low' or 'intermediate' ADNC levels or positive with 'high' ADNC levels. The [18F]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
Time Frame
At autopsy, until study completion with an average of 1 year
Title
Inter-reader agreement for the visual assessment of [18F]PI-2620 PET images
Description
Fleiss kappa will be used to measure the inter-reader agreement for the visual assessment of [18F]PI-2620 PET images.
Time Frame
Baseline scan

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Audrey Perrotin, PhD
Phone
+49 (0)30 461 1246 03
Email
clinicaltrials@life-mi.com
First Name & Middle Initial & Last Name or Official Title & Degree
Aleksandar Jovalekic, PhD
Phone
+49 (0)30 461 1246 03
Email
clinicaltrials@life-mi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alireza Atri, MD, PhD
Organizational Affiliation
Banner Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrew Stephens, MD, PhD
Organizational Affiliation
Life Molecular Imaging
Official's Role
Study Director
Facility Information:
Facility Name
Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Individual Site Status
Recruiting
Facility Name
Banner Sun Health Research Institute
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85352
Country
United States
Individual Site Status
Recruiting
Facility Name
Sutter Health
City
San Francisco
State/Province
California
ZIP/Postal Code
94114
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Galiz Research
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Recruiting
Facility Name
ClinCloud Research
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Individual Site Status
Recruiting
Facility Name
K2 Medical Research
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Individual Site Status
Recruiting
Facility Name
Verus Clinical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Individual Site Status
Recruiting
Facility Name
Miami Jewish Health Systems
City
Miami
State/Province
Florida
ZIP/Postal Code
33137
Country
United States
Individual Site Status
Recruiting
Facility Name
The Roskamp Institute
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34243
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Charter Research
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32792
Country
United States
Individual Site Status
Recruiting
Facility Name
Headlands Research
City
Plymouth
State/Province
Massachusetts
ZIP/Postal Code
02360
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Velocity Clinical Research
City
East Syracuse
State/Province
New York
ZIP/Postal Code
13057
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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[18F]PI-2620 Phase 3 Histopathological Study

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