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Proof of Mechanism Study to Evaluate Binding of Alfa-synuclein

Phase 1
Completed
Conditions
Parkinson Disease
Multisystem Atrophy
Healthy Volunteer
Interventions
Registration Number
NCT05274568
Lead Sponsor
Invicro
Brief Summary

The overall goal of this protocol is to:

Evaluate \[18F\]UCB-2897 as an α-synuclein targeted radiopharmaceutical.

The primary objective is:

• Confirm a specific α -synuclein signal with \[18F\]UCB-2897 in participants with PD and/or MSA relative to healthy volunteers

Secondary and exploratory objectives are:

* Determine the safety and tolerability of microdose \[18F\]UCB-2897

* Evaluate preliminary dosimetry of \[18F\]UCB-2897

Additional exploratory objectives are:

* Determine the pharmacokinetics / metabolism of \[18F\]UCB-2897

* Determine the optimal imaging protocol for \[18F\]UCB-2897

Detailed Description

This is a first in human \[FiH\], open-label study to assess the imaging characteristics, kinetics, and safety of \[18F\]UCB-2897 in participants with MSA, participants with PD, and healthy participants. Up to 2 participants with MSA, up to 8 participants with PD, and up to 5 healthy volunteers will be enrolled from the available database at Invicro, through advertising, and through physician referral. Participants will be enrolled in 2 parts that may be run concurrently: Part A (up to 2 participants with PD and up to 2 participants with MSA) and Part B (up to 6 participants with PD and up to 5 healthy volunteers). Data will be reviewed on an ongoing basis throughout the study, at least at the end of Part A.

All participants will attend the following (with exceptions noted):

* Screening

* \[18F\]UCB-2897 positron emission tomography (PET) Imaging Visit (including brain PET imaging or whole-body PET imaging)

* Follow-up Phone Call

* Amyloid PET Imaging Visit (not performed for all participants)

* DaTscan single photon emission computed tomography (SPECT) Imaging Visit (not performed for all participants)

During Screening, participants will undergo assessments to confirm study eligibility, including an MRI scan (unless a previously acquired approved scan is available) for participants who will have brain PET imaging. Participants with MSA and PD will also have a DaTscan SPECT scan during Screening (unless a previously acquired approved scan is available).

Within 4 weeks of the start of Screening, participants will attend a \[18F\]UCB-2897 PET Imaging Visit. Participants with MSA, participants with PD, and up to 2 healthy volunteers will undergo brain PET imaging, including one injection of \[18F\]UCB-2897, one brain PET scan lasting up to 2 hours, and arterial blood sampling. If the participant does not consent to arterial blood sampling or the study team deems it appropriate based on emerging data, venous blood samples may be collected in lieu of arterial blood samples. Brain PET imaging and blood data will be used to assess α-synuclein binding by \[18F\]UCB-2897. Up to 3 healthy volunteers will undergo whole-body PET imaging assessments, including one injection of \[18F\]UCB-2897, a series of whole-body PET scans lasting up to 6 hours, and urine collection. Whole-body PET imaging and urine samples will be assessed for a preliminary evaluation of \[18F\]UCB-2897 dosimetry. During PET imaging (both brain and whole-body), safety assessments will be performed to evaluate the safety and tolerability of \[18F\]UCB-2897, including ECGs, physical and neurological examinations, clinical laboratory samples, and vital sign measurements.

A Follow-up Phone Call to the participant will be conducted 4 days (± 2 days) post-injection of \[18F\]UCB-2897 to confirm participant well-being and to collect information about any new adverse events (AEs).

If the study team considers that further investigation on potential cross-binding with beta (β)-amyloid is needed, participants with MSA or PD will attend an Amyloid PET Imaging Visit and have amyloid PET imaging performed with an approved amyloid tracer (unless a previously acquired approved scan is available). Additionally, if needed for further interpretation of data, healthy volunteers who received brain PET imaging may have a DaTscan SPECT scan (unless a previously acquired approved scan is available).

When the participant completes his or her final study visit, the participant will be formally released from the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
5
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
[18F]UCB-2897[18F]UCB-2897Administration of Investigational Agent: Study center personnel will administer \[18F\]UCB-2897 as an IV injection. Prior to PET imaging, participants will have an IV catheter (for radiopharmaceutical administration) inserted according to standard clinical practice. Each participant will receive a single injection of \[18F\]UCB-2897. \[18F\]UCB-2897 will be injected IV at a dose of not more than 10 mCi, with a maximum mass dose of 10 μg and maximum volume of 10 mL. The injection will be followed by a 10 mL saline flush. Qualified study staff will accompany participants during PET imaging procedures.
Primary Outcome Measures
NameTimeMethod
Quantitative analysis of [18F]UCB-2897 brain PET scansDay 1: PET Imaging Visit

\[18F\]UCB-2897 uptake and kinetics will be examined in the MSA, PD, and healthy volunteer groups descriptively and quantitatively to describe the α-synuclein deposition as measured by \[18F\]UCB-2897 across multiple brain regions.

Whole-body Biodistribution Outcome Measures[18F]UCB-2897 PET Imaging Visit

For whole-body biodistribution, total source organ counts over time based on an individualized VOI template will be used to determine radiation absorbed dose estimates and whole-body effective doses based on the MIRD methodology.

Safety Outcome MeasuresScreening, pre-injection, and at the completion of imaging

Safety will be evaluated throughout the study. Safety will be evaluated by assessing incidence and severity of AEs, results from measurements of vital signs and ECGs, results from measurements for parameters of hematology, clinical chemistry, and urinalysis.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Invicro

🇺🇸

New Haven, Connecticut, United States

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