[18F]ACI-19626 PET in TDP-43 Proteinopathies

Early Phase 1

Recruiting

• Conditions: Frontotemporal Dementia (FTD); Amyotrophic Lateral Sclerosis (ALS); Alzheimer's Disease (AD); TDP-43 Proteinopathies; Suspected Limbic Predominant Age-related TDP-43 Encephalopathy (LATE)

• Registration Number: NCT06891716
• 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 TDP-43 \[involved in rare forms of dementia such as frontotemporal dementia (FTD) and in amyotrophic lateral sclerosis (ALS)\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-19626. Both healthy people and people with (suspected) TDP-43 accumulation will participate to this trial.

The main questions it aims to answer are:

* whether \[18F\]ACI-19626 is safe and well tolerated when injected into participants

* whether \[18F\]ACI-19626 reliably detects abnormal TDP-43 in the brain using PET technique.

* whether there are differences in the amount of this protein between people with diseases related to TDP-43 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 MRI in some cases).

* Visit the clinic to receive the tracer \[18F\]ACI-19626 intravenously and be scanned in a PET scanner, during which blood will be collected.

* Receive a phone call from the clinic 2 to 4 days 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, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible.

Detailed Description

This trial aims to evaluate the effects (i.e. safety and uptake) of a new radiotracer molecule. Study participants will take part in the study by attending two to three study visits over a period of up to 3 months (from the screening visit up to the last study visit).

The study consists of three parts in which a total of up to 45 participants may be included:

Part 1 may include in total up to 15 participants:

* up to 5 healthy controls (HCs)

* up to 5 symptomatic progranulin gene (GRN) and up to 5 symptomatic chromosome 9 open reading frame 72 (C9orf72) mutation carriers with FTD (including prodromal) either with or without motor neuron disease (MND) characteristics.

If the safety and dosimetry are satisfactory in the first subjects and sufficient data are obtained from this part, Part 2 may be initiated.

Part 2 may include in total up to 30 participants including:

* up to 25 patients with TDP-43 proteinopathies: up to 10 additional mutation carriers (including other mutations than GRN and C9orf72, and/or asymptomatic carriers) with FTD (including prodromal) either with or without MND characteristics; up to 10 sporadic or genetic (excluding mutations with known absence of TDP-43 pathology, e.g. Superoxide Dismutase 1 (SOD1) or fused in sarcoma protein gene (FUS)) ALS; up to 10 suspected TDP-43 related sporadic FTD or FTD-MND; up to 5 patients with other neurodegenerative diseases, e.g. AD or suspected Limbic-Predominant Age-related TDP-43 Encephalopathy (LATE) pathology

* up to 5 additional HVs may also be imaged, if necessary, to enable a better distinction of brain binding in this population compared to the population of subjects with TDP-43 proteinopathies

Part 3 aims to assess test-retest reliability. Up to 5 participants from Part 1 and/or Part 2 will have an additional scan within 1 month after their first scan to determine test-retest reliability.

Study Timeline

• Study Start: 2025-01-21
• Status Verified: 2025-03
• Study First Submitted: 2025-03-18
• Study First Submitted QC: 2025-03-18
• Last Update Submitted: 2025-03-18
• Study First Posted: 2025-03-24
• Last Update Posted: 2025-03-24
• Primary Completion: 2026-11
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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 or severe) and causal relationship (unrelated, unlikely, possibly or probably related)	From Informed Consent Signature (screening) to safety phone call after PET scan (i.e. up to 3 months in total)
Number of participants with clinically significant changes in vital signs measurements	During PET scan visit (i.e. at Day 0): before [18F]ACI-19626 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-19626.
Brain uptake of the tracer [18F]ACI-19626	At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection	\[18F\]ACI-19626 brain uptake in relevant regions of interest of the brain will be measured with PET scan and the mean of each group (participants with TDP-proteinopathies and healthy controls) will be calculated.
Assessment of the optimal kinetic model quantification of [18F]ACI-19626 tracer uptake	At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection	The selection of the optimal kinetic model will be done based on the Akaike's information criterion
Radiation dosimetry after one [18F]ACI-19626 PET scan	At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection	The radiation dose absorbed by relevant vital organs and the total effective dose will be measured, and the mean of scanned participants will be calculated

Secondary Outcome Measures

Name	Time	Method
Assessment of simplified methods to quantify brain uptake of the tracer [18F]ACI-19626	At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection	The validity of simplified reference tissue models will be assessed by determining correlation coefficients with corresponding outcome parameters from the optimal tracer full kinetic model
Variability of the tracer brain uptake between two [18F]ACI-19626 PET scans (test/retest)	At the first [18F]ACI-19626 PET scan and the second [18F]ACI-19626 PET scan (i.e. up to 1 month)	The repeatability/reliability of the \[18F\]ACI-19626 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-19626 PET scan for each participant in study Part 3, and the mean will be calculated.

Trial Locations

Locations (1)

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands