Establishing 18F PMPBB3 (APN 1607) PET Imaging Markers for Diagnosis of Tauopathy Parkinsonism Syndromes

Establishing 18F PMPBB3 (APN 1607) PET Imaging, Genetic and Plasma Biomarkers for Risk Identification, Disease Progression and Prognosis of Tauopathy Related Parkinsonism s Yndromes

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The diagnosis of PD is primarily based on clinical presentations while the pathology stage of a-synuclein containing Lewy body deposition has already advanced. In addition to PD, there is another group of patients presenting with parkinsonism features mixed with other neurodegenerative symptoms. Pathologically, patients with these PD-mimicking parkinsonism syndromes, such as progressive supranuclear palsy (PSP), corticobasal degeneration disorders (CBGD) and frontotemporal dementia (FTD) with/without parkinsonism, have 4 repeat paired helical filament forms of tau protein (4R PHF-tau) aggregations in the neurons. Patients with these tauopathy related parkinsonism-plus syndromes could initially present as PD symptoms but will have a more deliberating disease course and combine with other systems degeneration. These patients are often a substantial diagnostic challenge to clinicians. Therefore, there is an urgent need to develop reliable imaging and biofluid biomarkers for differentiating patients with PD and variable parkinsonism-plus syndromes.

Recently, new generation of novel radiotracer 18F-PMPBB3 (APN-1607), which can be labeled with 4R PHF-tau without significant off-target binding, has been successfully developed. Therefore, this study will enroll 150 participants, including 30 healthy controls, 30 PD patients, and 60 patients with different parkinsonism-plus syndromes (including 10 patients with multiple system atrophy, 10 patients with progressive supranuclear palsy, 10 patients with cortical basal syndrome and 30 patients with frontotemporal dementia), and 30 patients with mild cognitive decline (MCI) or Alzheimer's disease (AD). All participants will receive complete neurological examination, 18F-PMPBB3 (APN-1607) PET, brain MRI scans, plasma markers for total/phosphorylated tau, a-synuclein and Ab42/Ab40 and genetic markers covering MAPT、SNCA、LRRK2、GBA and APOE genes. We aim to explore:

1. Whether 18F-PMPBB3 (APN-1607) can differentiate patients with tauopathy (PSP, CBGD, FTD, MCI and AD) and synucleinopathy (PD, MSA).
2. Whether the distribution of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to disease severity, progression, and prognosis in patients with tauopathy.
3. Whether the loading of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to plasma levels of total/phosphorylated tau.
4. Determine specific genetic susceptibility sub-groups are more vulnerable to tau deposition detected by 18F-PMPBB3 (APN-1607) in patients with tauopathy.

The research results will help to understand the potential of 18F-PMPBB3 (APN-1607) as an imaging biomarker for diagnosis, severity and therapeutic assessment tool for patients with tauopathy.

Study Overview

• Status: Completed
• Conditions: Tau Distributions in Patients With Tauopathy Using APN-1607 PET Scan
• Intervention / Treatment: Diagnostic test: 18F-PMPBB3 (APN-1607) PET imaging

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Patients fulfill the criteria of United Kingdom Brain Bank Diagnostic Criteria of "possible" or "probably" PD.
3. Patients fulfill the criteria of MDS consensus criteria of "possible" or "probably" MSA.
4. Patients fulfill the criteria of NINDS-SPSP clinical criteria for the diagnosis of PSP "as possible" or "probably" PSP, and healthy volunteer with no clinically relevant finding on physical examination at screening visit.
5. Patients fulfill the criteria of Work Group on Frontotempotal Dementia and Pick's Disease of "possible" or "probably" FTD.
6. Patients fulfill the Armstrong's criteria of "possible" or "probably" CBGD.
7. Patients fulfill the National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup for clinical diagnostic guidelines (NIA-AA-C) for MCI.
8. Patients fulfill the National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup for clinical diagnostic guidelines (NIA-AA-C) for AD.
9. Neurologically normal controls.
10. Age range 20-90 years

Exclusion Criteria:

1. Implantation of metal devices including cardiac pacemaker, intravascular metal devices.
2. Major systemic diseases including coronary arterial disease, heart failure, uremia, hepatic failure, prominent strokes, acute myocardial infarction, poorly controlled diabetes, previous head injury, intracranial operation, hypoxia, sepsis or severe infectious diseases
3. Major psychiatric disorders, drug or alcohol abuse and major depression
4. Pregnant women or breast- feeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receving 18F-PMPBB3 (APN-1607) PET imaging; Single arm, open label	Diagnostic test: 18F-PMPBB3 (APN-1607) PET imaging; Name: 18F-PMPBB3 (APN-1607, MNI-958, or APN-0000455); Dosage form: injection form; Strength: 5mCi/dose; Dosage and administration: 5mCi, intravenous injection; Mechanism of action (if known): bind to tau protein in the brain; Pharmacological category: radiopharamceutical

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The distribution of tau measured by Standardized Uptake Value Ratio (SUVR) as Assessed by 18F-PM-PBB3 tau PET Scan	Tau Distribution among patients with parkinsonism-plus syndromes, Parkinson's disease (PD), Alzheimer's disease (AD) spectrum, and normal controls measured by Standardized Uptake Value Ratio (SUVR) as Assessed by 18F-PM-PBB3 tau PET Scan	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of tau measured by SUVR as assessed by 18F-PM-PBB3 tau PET Scan as disease severity in patients with tauopathy parkinsonism-plus syndrome	The correlation between Tau distribution among patients with tauopathy parkinsonism-plus syndrome with clinical severity.	1.5 years
The amount of tau measured by SUVR as assessed by 18F-PM-PBB3 tau PET Scan as disease progression in patients with tauopathy parkinsonism-plus syndrome.	The correlation between Tau distribution among patients with tauopathy parkinsonism-plus syndrome with clinical progression speed.	1.5 years
To correlate the loading of tau deposition detected by 18F-PMPBB3 (APN-1607) correlate to plasma levels of total/phosphorylated tau.	The correlation between Tau distribution among patients with tauopathy parkinsonism-plus syndrome with plasma levels of total/phosphorylated tau.	1.5 years
To determine specific genetic susceptibility sub-groups are more vulnerable to tau deposition detected by 18F-PMPBB3 (APN-1607) in patients with tauopathy.	The correlation between Tau distribution among patients with tauopathy parkinsonism-plus syndrome with genetic variants of candidate genes.	1.5 years
Safety endpoints - ECG	Changes of electrocardiography (ECG) QT Interval before and after receiving 18F-PMPBB3 (APN-1607) scans.	1.5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Any discomfort after receiving 18F-PMPBB3 (APN-1607) scans.	1.5 years
Safety endpoints-Vital signs	Changes of blood pressure (changes of SBP >=20 mmHg) before and after receiving 18F-PMPBB3 (APN-1607) scans.	1.5 years
Safety endpoints-adverse event assessments	Any discomfort after receiving 18F-PMPBB3 (APN-1607) scans.	1.5 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chin-Hsien Lin, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Actual): September 2, 2024
• Study Completion (Actual): September 2, 2024

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Tau
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Parkinsonian Disorders; Tauopathies
• Other Study ID Numbers: 202006181MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No