Proof of Mechanism Study to Evaluate Binding of Alfa-synuclein

NCT05274568 | Completed Phase 1 FDA Drug

• 1 other identifier: 10616
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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

Conditions

Parkinson Disease; Multisystem Atrophy; Healthy Volunteer

Outcome Measures

Primary Outcomes (3)

• Quantitative analysis of [18F]UCB-2897 brain PET scans

  \[18F\]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.

  Day 1: PET Imaging Visit

• Whole-body Biodistribution Outcome Measures

  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.

  [18F]UCB-2897 PET Imaging Visit

• Safety Outcome Measures

  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.

  Screening, pre-injection, and at the completion of imaging

Study Arms (1)

[18F]UCB-2897

EXPERIMENTAL

Administration 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.

Drug: [18F]UCB-2897

Interventions

[18F]UCB-2897 DRUG

Investigational Agent: \[18F\]UCB2897 is a clear solution formulated for intravenous (IV) injection. The product \[18F\]UCB2897is delivered in normal saline (0.9 % sodium chloride \[NaCl\]) formulated with the intent to contain approximately 3.3 % (v/v) ethanol (EtOH), polysorbate-80 (PS-80, 3.73 μL/mL) and sodium ascorbate (4.67 mg/mL). The final product bears a label with the following items: total activity (mCi), volume (mL), strength (mCi/mL), calibration date and time, batch number, and shelf life. \[18F\]UCB2897 will be stored at ambient temperature in its original container.

[18F]UCB-2897

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is able to provide informed consent, which must be obtained before any study procedures are performed.
• Female participants must not be of childbearing potential, or if they are of childbearing potential must agree to use contraception and not donate eggs.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (ie, removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the principal investigator (PI) (eg, Müllerian agenesis).
• Women of childbearing potential must commit to remain abstinent (refrain from heterosexual intercourse) or use 2 forms of birth control, 1 of which is a barrier contraception method, for the duration of the study and 30 days after study completion. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• Women of childbearing potential must commit to not donate ova for the duration of the study and 30 days after study completion.
• Male participants with partners of childbearing potential must commit to the use of 2 methods of contraception, 1 of which is a barrier method for male participants for the study duration and 90 days after study completion.
• Male participants must not donate sperm for the study duration and for 90 days after study completion.
• Willing and able to cooperate with study procedures.
• For participants who will have arterial cannulation performed, adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test) and blood clotting (Prothrombin Time \[PT\] and Partial Thromboplastin Time \[PTT\]).
• If participant takes bupropion, participant must agree to hold this medication for at least 12 hours prior to DaTscan imaging (if performed).
• OTC medication (except acetaminophen), herbal supplements, dietary supplements, or vitamins approved by the Investigator, must be stable within 2 weeks prior to initial dosing.
• Males and females aged ≥ 50 years.
• Diagnosis of probable MSA, according to Consensus Clinical Diagnostic Criteria for MSA and a consistent MRI scan performed either at Screening or previously acquired.
• Evidence of dopamine transporter (DaT) deficit on DaTscan performed either as part of Screening or previously acquired.
• Medications taken for symptomatic treatment must be maintained on a stable dosage regimen for at least 30 days before Screening Visit.

You may not qualify if:

• Pregnant, lactating or breastfeeding.
• Current or prior history of any alcohol or drug abuse in the past 2 years to be verified by urine drug screen.
• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
• History of immunodeficiency diseases, including a positive HIV test result.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result.
• Known history of hypersensitivity, including hypersensitivity to the active substances used for DaTscan, \[18F\]UCB2897, and/or \[18F\]florbetapir or derivatives, or to any of the associated excipients.
• Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Unsuitable veins for repeated venipuncture.
• Are claustrophobic or otherwise unable to tolerate the imaging procedure.
• MRI with clinically significant structural abnormalities, other than those expected for MSA or PD for those participants.
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, central nervous system (CNS) aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
• Participant has received an investigational drug within 30 days or five half-lives prior to Day 1, whichever is longer.
• Participant has received treatment with a drug, antibody or vaccine targeting α-synuclein.
• Prior participation in other research protocols, clinical care, or occupational exposure during the past year that would result in radiation exposure to an effective radiation dose exceeding the acceptable annual limit established by the US Federal Guidelines (effective dose of 50 mSv, including the procedures in this clinical protocol).
• For participants receiving DaTscan imaging, ongoing treatment with methylphenidate, modafinil, metoclopramide, alpha methyldopa, reserpine, or amphetamine derivative is prohibited 24 hours or during a period corresponding to 5 half-lives of the compound, whichever longer, prior to DaTscan imaging.

Sponsors & Collaborators

• Invicro: lead

Study Sites (1)

Invicro

New Haven, Connecticut, 06510, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Parkinson Disease; Multiple System Atrophy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases

Study Officials

• David Russell, MD, Ph.D

  Principal Investigator

  PRINCIPAL INVESTIGATOR

• Joyce Gibbons, PA-C

  Sub-Investigator

  PRINCIPAL INVESTIGATOR

• Amy Knorr, MD

  Sub-Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: March 10, 2022
• Study Start: January 31, 2022
• Primary Completion: October 25, 2023
• Study Completion: October 25, 2023
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)