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

NCT06891716 | Recruiting Early Phase 1

• 2 other identifiers: ACI-19626-FTD-23012024-513097-21-00
• Study Type: interventional
• Target: 45
• 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 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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• 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

  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.

  During PET scan visit (i.e. at Day 0): before [18F]ACI-19626 injection and after the PET scan is completed

• Brain uptake of the tracer [18F]ACI-19626

  \[18F\]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.

  At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection

• Assessment of the optimal kinetic model quantification of [18F]ACI-19626 tracer uptake

  The selection of the optimal kinetic model will be done based on the Akaike's information criterion

  At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection

• Radiation dosimetry after one [18F]ACI-19626 PET scan

  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

  At the time of the [18F]ACI-19626 PET scan (i.e. at Day 0): 0-90 minutes after injection

Secondary Outcomes (2)

• 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

• 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)

Study Arms (2)

Participants with suspected TDP-43 proteinopathies

EXPERIMENTAL

The study population will be composed of participants with suspected TDP-43 proteinopathies

Other: [18F]ACI-19626

Healthy controls

ACTIVE COMPARATOR

The study population will be composed of healthy controls.

Other: [18F]ACI-19626

Interventions

[18F]ACI-19626 OTHER

\[18F\]ACI-19626 is an intravenously administered radioactive imaging agent being studied as a potential positron emitting radiopharmaceutical for in vivo imaging of TDP-43 deposits.

Healthy controls; Participants with suspected TDP-43 proteinopathies

Eligibility Criteria

• Age: 40 Years - 70 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 (IC), which must be obtained before any assessment is performed.
• Female subjects must not be of childbearing potential, or if they are of childbearing potential to agree to use reliable contraception method(s) and not donate eggs for 30 days after the PET scan. Subjects without documentation of non-childbearing potential will perform serum pregnancy testing at screening and urine pregnancy test before the PET scan. 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 (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the PI (e.g., Müllerian agenesis). Women of childbearing potential must commit to remain abstinent (refrain from heterosexual intercourse) or use a reliable form of birth control (e.g. a barrier, hormonal contraception method or intrauterine device), during the study and until 30 days after the last PET scan. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. Women of childbearing potential must commit to not donate ovum during the study and until 30 days after the last PET scan.
• Male subjects with their partners of childbearing potential must commit to the use of a barrier method of contraception during the study and until 90 days after the last PET scan.
• Male subjects must commit to not donate sperm during the study and until 90 days after the last PET scan.
• Willing and able to cooperate with study procedures.
• Ability to tolerate lying in the scanner for up to 90 minutes without excessive movements sufficient to cause significant motion artifact on the PET scans, or if necessary up to 120 minutes with a break.
• For subjects receiving arterial cannulation, adequate circulation to the hand for safe placement of arterial line and coagulation (International Normalized Ratio \[INR\], Prothrombin Time \[PT\] and Partial Thromboplastin Time \[PTT\]).
• Males and females aged 40-70 years.
• Healthy with no clinically relevant finding on physical and neurological examination at Screening and upon reporting to the clinic for the \[18F\]ACI-19626 Imaging Visit.
• No family history of TDP-43 proteinopathies, including FTD, ALS, or other early-onset neurological disease associated with dementia and/or movement disorders.
• No personal history of clinically significant neurological and/or psychiatric disorders.
• No evidence of neurodegeneration or other neurological pathology on magnetic resonance imaging (MRI) performed either as part of Screening or on previously acquired MRI scan (within 6 months prior to signing consent).
• Montreal Cognitive Assessment (MoCA) score ≥ 26.
• No cognitive or behavioural impairment as judged by the PI.
• Males and females aged ≥ 40 years.

You may not qualify if:

• 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 condition.
• Known history of hypersensitivity, including hypersensitivity to the active substances used for \[18F\]ACI-19626 or derivatives, or to any of the associated excipients.
• 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 (including the procedures in this clinical protocol).
• Pregnant or lactating.
• 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.
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.
• Treatment with any antihemostasis medication (e.g., warfarin, heparin, thrombin inhibitors, Factor Xa inhibitors, streptokinase, urokinase, tissue plasminogen activators) within 2 weeks of the planned arterial cannula placement (if performed) of either the baseline or retest imaging.
• Anaemia (for subjects undergoing arterial cannulation) considered clinically significant by the PI
• Coagulopathies
• Loss or donation of blood over 500 mL within four months prior to study visits for subjects undergoing arterial cannulation
• Subject has received an investigational drug within the last 30 days or 5 half-lives prior to the screening assessments, whichever is longer unless there is documented evidence that the subject was treated with placebo only.
• Prior participation in DMT clinical trials which could interfere with the TDP-43 protein itself or its metabolism, including but not limited to gene therapy, unless there is documented evidence that the subject was treated with placebo only.
• MRI scan showing structural evidence of alternative pathology not consistent with TDP-43 proteinopathies which could cause the subject's symptoms.

Sponsors & Collaborators

• AC Immune SA: lead
• Amsterdam UMC, location VUmc: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

MeSH Terms

Conditions

Frontotemporal Dementia; Amyotrophic Lateral Sclerosis; TDP-43 Proteinopathies; Alzheimer Disease

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Spinal Cord Diseases; Motor Neuron Disease; Neuromuscular Diseases; Tauopathies

Study Officials

• Elsmarieke van de Giessen, MD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

• Clinical Lead

  AC Immune SA

  STUDY DIRECTOR

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: January 21, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 24, 2025

Record last verified: 2025-03

Locations

NL (1)