Evaluation of Imaging Characteristics of [18F]PI-2620 PET in AD and PSP Patients Using High and Low Specific Activity

An Open Label, Single Center Study to Evaluate the Safety and Imaging Characteristics of [18F]PI-2620 as PET Radioligand for Imaging Tau Deposition in the Brains of Patients With Mild to Moderate Alzheimer's Disease (AD) and Patients With Progressive Supranuclear Palsy (PSP) After i.v. Application of [18F]PI-2620 With High and Low Specific Activity

This is an open-label study without randomisation. All eligible patients will receive two administrations of the investigational imaging agent [18F]PI-2620 at a radioactive dose of 185 MBq, one with high specific activity (≤ 5 µg tracer mass dose), another one with low specific activity (40-50 µg tracer mass dose).

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Progressive Supranuclear Palsy
• Intervention / Treatment: Drug: [18F]-PI2620

Detailed Description

This is an open-label, single center study to visually assess and quantitatively compare brain PET images obtained after application of [18F]PI-2620 with different specific activities: 1) High specific activity (low mass dose): 185 MBq containing a maximum mass dose of ≤5 μg in up to 10 mL and 2) Low specific activity (high mass dose): 185 MBq containing a maximum mass dose of 40-50 μg in up to 10 mL).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany
    • Department of Nuclear Medicine, University Hospital Leipzig

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females aged 50-80 years
• Able to understand, sign and date written informed consent, which is confirmed by the judgment of the referring physician
• Written informed consent must be obtained before any assessment is performed
• Prior evaluable MRI
• Female patients must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause). If they are of child-bearing potential, must commit to use of a highly effective contraceptive measure for the duration of the study
• Male patients and their partners of childbearing potential must commit to the use of a highly effective method of contraception for a minimum of one week following each PET scan
• Male patients must commit to not donate sperm for a minimum of one week after each PET scan.

Inclusion Criteria for mild-moderate AD patients

• Patients with mild or moderate AD in accordance with NIA-AA guidelines 2011
• Have a CDR score of ≥ 0.5 at screening
• Have an MMSE score of ≤ 24 at screening
• Prior evaluable amyloid PET imaging confirming presence of beta-amyloid brain pathology
• Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before the [18F]PI-2620 PET imaging visits

Inclusion Criteria for patients with probable PSP

• Patients with a clinical diagnosis of probable PSP based on the Movement Disorder Society criteria (Höglinger et al., 2017).
• Have a PSP rating score between 20 - 60
• Medications taken for symptomatic treatment of PSP must be maintained on a stable dosage regimen for at least 30 days before the [18F]PI-2620 PET imaging visits

Exclusion Criteria (for all patients)

• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness equivalent to CTC v5.0 (common toxicity criteria) toxicities greater than grade 2
• Evidence of clinically significant disease that is expected to interfere with cognitive assessments or the ability to complete the study procedures
• Patient has received an investigational drug including treatments targeting amyloid-beta plaques or tau within 3 months of screening
• Pregnant (or intention of getting pregnant), lactating or breastfeeding
• MRI exclusion criteria include: Findings of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct >1 cm3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the Fluid-Attenuated Inversion Recovery (FLAIR) sequence that is >=20 mm in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with Central Nervous System (CNS) disease
• 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
• Unwilling and/or unable to cooperate with study procedures

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: Tau deposition in the brains of Alzheimer Disease and Progressive Supranuclear Palsy patients; All patients will receive two administrations of [18F]PI-2620 at a radioactive dose of 185 MBq, one with high specific activity (≤ 5 µg tracer mass dose), another one with low specific activity (40-50 µg tracer mass dose)

Drug: [18F]-PI2620; [18F]PI-2620 is a radioactive diagnostic agent being developed for the indication of PET imaging of the brain to detect tau pathology in adult patients who are being evaluated for neurodegenerative decline. All patients will receive two administrations of [18F]PI-2620 at a radioactive dose of 185 MBq, one with high specific activity (≤ 5 µg tracer mass dose), another one with low specific activity (40-50 µg tracer mass dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparability of visual assessment of PI-2620 tau PET images obtained after injection of high specific activity and low specific activity in AD and PSP patients.	PI-2620 tau PET images obtained with [18F]PI-2620 using high specific activity (185 MBq and ≤ 5 µg mass dose) and with [18F]PI-2620 using low specific activity (185 MBq and 40-50 µg mass dose) in AD and PSP patients will be visually analyzed. Visual analysis of the tau signal pattern will be compared for high and low specific activity images within the same subject.	4-54 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparability of quantitative assessment of PI-2620 tau PET images obtained after injection of high specific activity and low specific activity in AD and PSP patients.	PI-2620 tau PET images obtained with [18F]PI-2620 using high specific activity (185 MBq and ≤ 5 µg mass dose) and with [18F]PI-2620 using low specific activity (185 MBq and 40-50 µg mass dose) in AD and PSP patients will be quantitatively analyzed. Quantitative analysis of the tau signal pattern will be compared for high and low specific activity images within the same subject.	4-54 days
Number of adverse events	Safety will be evaluated by collection of Adverse Events.	From injection of [18F]PI-2620 until up to 6 days after injection

Collaborators and Investigators

• Sponsor: Life Molecular Imaging GmbH
• Collaborators: Life Molecular Imaging SA
• Investigators: Study Director: Andrew Stephens, MD, PhD, Life Molecular Imaging GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): October 26, 2022
• Study Completion (Estimated): September 1, 2023

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer Disease; Progressive Supranuclear Palsy; Tau PET; [18F]PI-2620; Mass dose; Specific activity
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Neurocognitive Disorders; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Paralysis; Ophthalmoplegia; Alzheimer Disease; Supranuclear Palsy, Progressive
• Other Study ID Numbers: LMT-01-01-19

Drug and device information, study documents

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