[18F]ACI-15916 PET in α-synucleinopathies

NCT06891703 | Recruiting Early Phase 1

• 2 other identifiers: ACI-15916-PD-24012024-515664-31-00
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test whether we can reliably and safely measure the accumulation of pathological protein α-synuclein \[involved in some diseases such as Parkinson's disease, Lewy body dementia and Multiple System Atrophy (MSA), collectively named α-synucleinopathies\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-15916. Both healthy people and people with (suspected) α-synuclein pathology will participate to this trial. The main questions it aims to answer are:

• whether \[18F\]ACI-15916 is safe and well tolerated when injected into participants
• whether \[18F\]ACI-15916 reliably detects α-synuclein in the brain using PET technique.
• whether there are differences in the amount of this protein between people with diseases related to α-synuclein accumulation in the brain and people without these diseases. Participants will:
• Visit the clinic to consent to their participation and to ensure they are eligible \[physical and neurological examinations, questionnaires, blood and urine tests, ECG and in some cases a MRI and a PET scan with a licensed tracer (\[18F\]FE-PE2I) to confirm or not the disease\].
• Visit the clinic to receive the tracer \[18F\]ACI-15916 intravenously and be scanned in a PET scanner, during which blood will be collected (and optionally spinal fluid).
• Receive a phone call from the clinic 1 week after the PET scan to report any symptoms and side-effects that they may be having. Some of the participants may be asked to come again to the clinic for a second PET scan with \[18F\]ACI-15916, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible. Some of the participants will participate in a specific part of the study to evaluate the distribution of the PET ligand in the whole body, with a similar visit schedule.

Conditions

Parkinson's Disease (PD); Multiple System Atrophy (MSA); Dementia With Lewy Bodies (DLB)

Outcome Measures

Primary Outcomes (3)

• Number of participants with Adverse Events (AEs) assessed by severity (mild, moderate, severe, life threatening, death) and causal relationship (not related, unlikely related, possibly related or related)

  From Informed Consent Signature (screening) to safety phone call after PET scan (i.e. up to 14 weeks in total)

• Number of participants with clinically significant changes in vital signs measurements

  Vital signs measurements will be performed after the PET scan is completed and will be compared with measurements performed before the injection of \[18F\]ACI-15916

  During PET scan visit (i.e. at Day 0): before [18F]ACI-15916 injection and after the PET scan is completed

• Brain uptake of the tracer [18F]ACI-15916

  \[18F\]ACI-15916 uptake in relevant regions of interest of the brain will be measured with PET scan and the mean of each group (participants with α-synucleinopathies and healthy volunteers) will be calculated

  At the time of the [18F]ACI-15916 PET scan (i.e. at Day 0): 0-93 minutes after injection

Secondary Outcomes (3)

• Assessment of simplified methods to quantify brain uptake of the tracer [18F]ACI-15916

  At the time of the [18F]ACI-15916 PET scan (i.e. at Day 0): 0-93 minutes after injection

• Variability of the tracer brain uptake between two [18F]ACI-15916 PET scans (test/retest)

  From the first PET scan (i.e. Day 0) to the second PET scan (i.e. Day 30)

• Radiation dosimetry after one [18F]ACI-15916 PET scan

  At the time of the [18F]ACI-15916 PET scan (i.e. at Day 0): 0-6 hours after injection

Study Arms (2)

Participants with suspected α-synucleinopathies

EXPERIMENTAL

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

Other: [18F]ACI-15916

Healthy volunteers

ACTIVE COMPARATOR

The study population will be composed of healthy volunteers

Other: [18F]ACI-15916

Interventions

[18F]ACI-15916 OTHER

\[18F\]ACI-15916 is an intravenously administered radioactive imaging agent being studied as a potential positron emitting radiopharmaceutical for in vivo imaging of α-synuclein deposits.

Healthy volunteers; Participants with suspected α-synucleinopathies

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is able to provide written informed consent, which must be obtained before any assessment is performed.
• Subjects must be able to understand and be willing to comply with study procedures, restrictions, and requirements.
• Body mass index is \> 18 and \< 31 kg/m2 and Bodyweight ≥ 50 kg and ≤ 100 kg.
• Female participants must not be of childbearing potential or agree to use highly effective methods of contraception.
• For subjects receiving arterial cannulation, an adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test).
• Males and females aged ≥ 20 at the time of signing the informed consent.
• Normal MRI and DAT PET or SPECT (except for Part 4 participants), as judged by the investigator.
• The subject is, in the opinion of the investigator, generally healthy based on the assessment of medical history, physical examination, vital signs, ECG, and the results of the hematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
• 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.
• Have a Montreal Cognitive Assessment (MoCA) score ≥ 26
• No cognitive impairment as judged by the PI or delegated physician.
• Males and females aged ≥ 40 at the time of signing the informed consent.
• Subjects diagnosed with any of the following:
• Idiopathic PD based on MDS criteria

You may not qualify if:

• Dementia with Lewy bodies (DLB)
• Diagnosis of possible or probable Multiple System Atrophy (MSA)
• Evidence of dopamine transporter deficit on DAT PET or SPECT imaging performed either as part of Screening or previously acquired (if not older than 6 months) and of good quality as judged by the investigator.
• Medications taken for symptomatic treatment of α-synucleinopathy must be maintained on a stable dosage regimen for at least 30 days before the Screening Visit.
• Female subjects pregnant, lactating or breastfeeding.
• Presence of psychiatric symptoms that may interfere with the objectives of the study, as judged by the investigator.
• Clinically significant concomitant disease or condition within 6 months prior to screening, that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant, or compromise the scientific quality of the study.
• History of brain surgery or any neurosurgical procedures. Subject has received treatment with a drug, antibody or vaccine targeting α-synuclein.
• Known or suspected drug, alcohol or other abuse, or positive urine drug screen which may interfere with the study objective, as judged by the investigator.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity as judged by the investigator.
• Subject is involved in the planning and/or conduct of the study (i.e. part of the study team)
• History of clinically significant cardio-or cerebrovascular, pulmonary, renal, hepatic, neurological, mental or gastrointestinal disorder or any other major disorder that may interfere with the objectives of the study, as judged by the investigator.
• History of and/or screening brain MRI scan (except for Part 4 subjects) indicative of, clinically significant abnormality including but not limited to prior haemorrhage or infarct or \>3 lacunar infarcts, except changes consistent with α-synucleinopathies for PD, MSA, DLB patients.
• Subjects being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower within 2 weeks of the planned arterial cannula placement (if performed) for either the baseline or retest imaging.
• Screening supine blood pressure \> 150 mm Hg (systolic) or \> 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is \> 150 mm Hg (systolic) or \> 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.

Sponsors & Collaborators

• AC Immune SA: lead
• Karolinska Institutet: collaborator

Study Sites (1)

Karolinska Institutet

Solna, Sweden

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Multiple System Atrophy; Lewy Body Disease

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; Dementia; Neurocognitive Disorders; Mental Disorders

Study Officials

• Andrea Varrone, Prof.

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AC Immune SA Clinical Trial Information

CONTACT

+41 21 34 59 121; clinicaltrials@acimmune.com

Study Design

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

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 24, 2025
• Study Start: March 20, 2025
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

SE (1)