Study to Evaluate a Potential PET Radioligand for Imaging Alpha-synuclein Deposits in the Brain

NCT06445465 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 9105
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this protocol is to evaluate \[18F\]MNI-1216 (also known as \[18F\]ACI-12589) as an α-synuclein targeted radiopharmaceutical in 3 parts as follows:

• Part 1: first in human (FiH) imaging
• Optional Part 2: expansion of FiH imaging
• Optional Part 3: retest imaging A total of up to 30 participants may be enrolled and participate in the study. Part 1 of the study will include up to 10 participants (target of up to 5 healthy volunteers and up to 5 participants with idiopathic Parkinson's Disease). There will be an ongoing review of study data in Part 1 to evaluate the characteristics of tracer binding and safety. If the study results are deemed adequate in Part 1, Part 2 and/or Part 3 may be initiated. The decision to initiate Part 3 may also include a review of data from Part 2, if Part 2 is performed and the data are available. If performed, Part 2 will include up to 20 participants, including health volunteers and participants with α-synucleinopathies to acquire additional tracer-related data. If performed, Part 3 will include up to 10 participants from in Part 1 and/or Part 2 (including health volunteers and participants with α-synucleinopathies) to evaluate the reliability of \[18F\]MNI-1216 (\[18F\]ACI-12589) Positron Emission Tomography (PET) imaging.

Conditions

Alpha-Synucleinopathy; Parkinson's Disease; Dementia With Lewy Bodies; Multisystem Atrophy

Outcome Measures

Primary Outcomes (2)

• Volume of distribution (VT) of [18F]MNI-1216 across multiple brain regions

  Volume of distribution (VT) across multiple brain regions will be measured and comparison between participants with α-synucleinopathies and healthy volunteers will be performed to visually and quantitatively assess brain uptake and pharmacokinetics of \[18F\]MNI-1216 (\[18F\]ACI-12589) as a PET imaging marker for α-synuclein pathology in individuals with α-synucleinopathies.

  up to 78 days

• Number of participants with [18F]MNI-1216-related adverse events as assessed by CTCAE

  Participants will be monitored to evaluate the safety of a single injection of \[18F\]MNI-1216 (\[18F\]ACI-12589). The following assessments will be performed to monitor participants for adverse reactions: * Clinical laboratory tests. * Vital signs. * Physical findings. * Electrocardiograms

  up to 78 days

Other Outcomes (2)

• Average variability across subjects

  up to 78 days

• Intraclass correlation (ICC) of test and retest scans

  up to 78 days

Study Arms (2)

Participants with α-synucleinopathies.

EXPERIMENTAL

The study population will be composed of participants with α-synucleinopathies.

Drug: [18F]MNI-1216

Healthy volunteers

ACTIVE COMPARATOR

The study population will be composed of health volunteers.

Drug: [18F]MNI-1216

Interventions

[18F]MNI-1216 DRUG

\[18F\]MNI-1216 is an intravenously administered radioactive imaging agent being studied as a potential positron emitting radiopharmaceutical for in vivo imaging of α-synuclein deposits.

Also known as: [18F]ACI-12589

Healthy volunteers; Participants with α-synucleinopathies.

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants is able to provide written informed consent, which must be obtained before any assessment is performed.
• Female participants must not be of childbearing potential, or agree to use contraception and not donate eggs if of childbearing potential. At the discretion of the Investigator, participants without documentation of non-childbearing potential may receive pregnancy testing.
• A woman is considered to be of childbearing potential if 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 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 ovum for the duration of the study and 30 days after study completion.
• Male participants and their 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 receiving arterial cannulation, adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test) and blood clotting (PT and PTT).
• If participant takes bupropion, participant must agree to hold this medication for at least 12 hours prior to DaTscan imaging (if performed).
• Males and females aged ≥ 21 years.
• Healthy with no clinically relevant finding on physical examination at Screening and upon reporting to the clinic for the \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit.
• No family history of α-synucleinopathy, including PD, or other early-onset neurological disease associated with dementia.
• No personal history of clinically significant neurologic and/or psychiatric disorders.
• No evidence of dopamine transporter deficit on DaTscan performed either as part of Screening or on previously acquired DaTscan (within 6 months prior to signing consent).

You may not qualify if:

• Evidence of dopamine transporter deficit on DaTscan performed either as part of Screening or on previously acquired DaTscan.
• Medications taken for symptomatic treatment of α-synucleinopathy must be maintained on a stable dosage regimen for at least 30 days before Screening Visit.
• Ability to tolerate lying in the scanner for up to \~180 minutes without excessive head or jaw tremor or dyskinesia sufficient to cause significant motion artifact on the PET scans.
• Current or prior history of any alcohol or drug abuse in the past 2 years.
• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
• Known history of hypersensitivity, including hypersensitivity to the active substances used for DaTscan, \[18F\]MNI-1216 (\[18F\]ACI-12589) and \[18F\]florbetapir or derivatives, or to any of the associated excipients.
• Participant has received an investigational drug within 30 days or five half-lives prior to the baseline assessments, whichever is longer.
• Prior participation in other research protocols or clinical care 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).
• Pregnant, lactating or breastfeeding.
• 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.
• MRI with clinically significant structural abnormalities.
• 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 treatment with a drug, antibody or vaccine targeting α-synuclein.
• 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
• AC Immune SA: collaborator

Study Sites (1)

Invicro

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Synucleinopathies; Parkinson Disease; Lewy Body Disease; Multiple System Atrophy

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Dementia; Neurocognitive Disorders; Mental Disorders; Primary Dysautonomias; Autonomic Nervous System Diseases

Study Officials

• David Russell, MD

  Invicro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study population will be composed of up to 30 subjects, including healthy volunteers and participants with α-synucleinopathies.

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: June 6, 2024
• Study Start: December 24, 2020
• Primary Completion: November 26, 2024
• Study Completion: November 26, 2024
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)