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

Early Phase 1

Recruiting

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

• Registration Number: NCT06891703
• Lead Sponsor: AC Immune SA

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.

Detailed Description

This is an open-label, first in human (FiH) positron emission tomography (PET) microdose study in patients with suspected α-synuclein pathology and healthy volunteers (HVs) using \[18F\]ACI-15916 as a novel radioligand. This study will be dedicated to qualification of the ligand \[18F\]ACI-15916 to measure α-synuclein pathology using PET investigations, including estimation of effective dose and test-retest reliability.

The study consists of four parts in which a total of up to 46 participants may be included:

* Part 1: Up to 5 HVs and up to 5 patients with Parkinson's Disease (PD) will be included.

* Part 2: Up to 30 additional subjects including: HV cases (maximum 10) and patients with α-synucleinopathies such as PD, Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).

* Part 3: Up to 10 participants from Part 1 and/or Part 2 will have a second PET measurement within one month after their initial PET measurement to evaluate test-retest variability and reproducibility.

* Part 4. Up to 6 HVs (3 female and 3 male) will undergo a whole-body PET-CT examination to estimate the effective dose after one administration of \[18F\]ACI-15916.

The four study parts can overlap.

The study consists of a screening period of up to 60 days to assess participants' eligibility, a PET scan with \[18F\]ACI-15916 along with arterial blood sampling, and a safety phone call following the scanning visit. For participants in Part 3, a second PET scan with \[18F\]ACI-15916 will be performed up to one month after the first scan to evaluate test-retest variability and reproducibility, followed by a new safety phone call. For subjects in Part 4 (dosimetry), no arterial blood sampling will be performed. The total study duration will be up to 10 weeks for Part 1, 2 and 4 participants and up to 14 weeks for Part 3 participants.

Study Timeline

• Study First Submitted: 2025-03-18
• Study First Submitted QC: 2025-03-18
• Study Start: 2025-03-20
• Study First Posted: 2025-03-24
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-09
• Primary Completion: 2026-03
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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)
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	\[18F\]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
Number of participants with clinically significant changes in vital signs measurements	During PET scan visit (i.e. at Day 0): before [18F]ACI-15916 injection and after the PET scan is completed	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

Secondary Outcome Measures

Name	Time	Method
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	Reference tissue models will be used to quantify the brain uptake of the tracer \[18F\]ACI-15916 using an appropriate reference region in the brain. The mean will be calculated for each group (healthy volunteers and α-synucleinopathies)
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)	The repeatability/reliability of the \[18F\]ACI-15916 brain uptake measures will be assessed by calculating the variability (percentage difference) of the tracer brain uptake between the first and the second \[18F\]ACI-15916 PET scan for each participant in study Part 3, and the mean will be calculated.
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	The radiation dose absorbed by relevant vital organs and the total effective dose will be measured for each participant of study Part 4, and the mean of scanned participants will be calculated

Trial Locations

Locations (1)

Karolinska Institutet; 🇸🇪 Solna, Sweden