Alpha-SynucleinopathyEarly Phase 1NCT06445465
Study to Evaluate a Potential PET Radioligand for Imaging Alpha-synuclein Deposits in the Brain
A Early Phase 1 study testing [18F]MNI-1216 in people with Alpha-Synucleinopathy and Parkinson's Disease, run by Invicro at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alpha-Synucleinopathy, Parkinson's Disease, Dementia With Lewy Bodies
- What is being tested?
- [18F]MNI-1216
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Dec 2020to 26 Nov 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Show all 29Show fewer
- 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).
- Additional Inclusion Criteria for healthy volunteers:
- 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).
- Have a Montreal Cognitive Assessment (MoCA) score ≥ 26.
- No cognitive impairment as judged by the PI.
- Additional Inclusion Criteria for Participants with α-synucleinopathy:
- Males and females aged ≥ 40 years.
- Participants diagnosed with any of the following:
- Idiopathic Parkinson's Disease
- Parkinson's Disease with genetic risk factor (except leucine-rich repeat kinase 2 [LRRK2] mutation)
- Dementia with Lewy Bodies
- Multisystem Atrophy
- A brain MRI consistent with a diagnosis of α-synucleinopathy, with no evidence of focal disease to account for the participant's neurological symptoms or MRI exclusion criteria listed below under "Exclusion Criteria".
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
- Treatment with any antihemostasis medication (eg, warfarin, heparin, thrombin inhibitors, Factor Xa inhibitors, streptokinase, urokinase, tissue plasminogen activators) within 2 weeks of the planned arterial cannula placement (if performed) for either the baseline or retest imaging.
- Additional Exclusion Criteria for Participants with α-synucleinopathy:
- Evidence of early frequent falls or eye movement abnormalities consistent with PSP.
- Individuals with known LRRK2 mutation (based on previous source documentation).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Study to Evaluate [18F]MNI-1216 ([18F]ACI-12589) as a Potential PET Radioligand for Imaging Alpha-synuclein Deposits in the Brain of Patients With Suspected Alpha-synuclein Pathology Compared With Healthy Volunteers
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.
Read the detailed description
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.
The specific objective for Parts 1, 2, and 3 is:
- To characterize [18F]MNI-1216 ([18F]ACI-12589) as a PET radioligand for imaging α-synuclein pathology.
The additional specific objectives for Part 1 and Part 2 are:
- 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 (including idiopathic PD) compared with corresponding data from healthy volunteer participants.
- To evaluate the safety of a single injection of [18F]MNI-1216 ([18F]ACI-12589).
The additional specific objectives for Part 3 are:
- To evaluate the reliability (test/retest) of [18F]MNI-1216 ([18F]ACI-12589) parameters in individuals with α-synucleinopathies and healthy volunteers.
- To evaluate the safety of up to 2 injections of [18F]MNI-1216 ([18F]ACI-12589).
For each subject participating in the study, the duration of study participation will be up to 78 days.
In Part 1 and Part 2 (if Part 2 is performed), screening assessments will occur within 30 days prior to the Baseline [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit (Day 1). If determined to be necessary by the study team, subjects may participate in an [18F]Florbetapir Imaging Visit up to 6 weeks following Day 1 (will be completed between Day 2 and Day 42). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following each imaging visit performed. In Part 3 (if performed), subjects will participate in a Retest [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit between Day 4 and Day 29 (within 3 days to 4 weeks) following the Baseline [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit (Day 1). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following the retest imaging visit, if performed.
- Conditions
- Alpha-Synucleinopathy, Parkinson's Disease, Dementia With Lewy Bodies, Multisystem Atrophy
- Being tested
- [18F]MNI-1216
- Medical subject headings
- Synucleinopathies, Parkinson Disease, Lewy Body Disease, Multiple System Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]MNI-1216Drug
Also called [18F]ACI-12589
[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.
| Study group | Role | What they receive |
|---|---|---|
| Participants with α-synucleinopathies. | Experimental | The study population will be composed of participants with α-synucleinopathies. Receives: Drug: [18F]MNI-1216 |
| Healthy volunteers | Active comparator | The study population will be composed of health volunteers. Receives: Drug: [18F]MNI-1216 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: up to 78 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start24 Dec 2020
- Primary completion26 Nov 2024
- Study completion26 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha-SynucleinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study population will be composed of up to 30 subjects, including healthy volunteers and participants with α-synucleinopathies.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Invicro
- Sponsor type
- University, hospital or other
- Collaborators
- AC Immune SA
- Responsible party
- Sponsor
- Investigators
- David Russell, MD, Principal investigator, Invicro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06445465
- Sponsor's protocol ID
- 9105
- Status last verified
- Feb 2025
- First submitted
- 23 Apr 2024
- Last updated
- 19 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study to Evaluate [18F]MNI-1216 ([18F]ACI-12589) as a Potential PET Radioligand for Imaging Alpha-synuclein Deposits in the Brain of Patients With Suspected Alpha-synuclein Pathology Compared With Healthy Volunteers
- ClinicalTrials.gov ID
- NCT06445465
- Acronym / sponsor ID
- 9105
- Conditions
- Alpha-Synucleinopathy, Parkinson's Disease, Dementia With Lewy Bodies, Multisystem Atrophy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- InvicroUniversity, hospital or other
- Collaborators
- AC Immune SA
- Study start
- 24 Dec 2020 (actual)
- Primary completion
- 26 Nov 2024 (actual)
- Study completion
- 26 Nov 2024 (actual)
- First posted
- 6 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
The specific objective for Parts 1, 2, and 3 is:
- To characterize [18F]MNI-1216 ([18F]ACI-12589) as a PET radioligand for imaging α-synuclein pathology.
The additional specific objectives for Part 1 and Part 2 are:
- 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 (including idiopathic PD) compared with corresponding data from healthy volunteer participants.
- To evaluate the safety of a single injection of [18F]MNI-1216 ([18F]ACI-12589).
The additional specific objectives for Part 3 are:
- To evaluate the reliability (test/retest) of [18F]MNI-1216 ([18F]ACI-12589) parameters in individuals with α-synucleinopathies and healthy volunteers.
- To evaluate the safety of up to 2 injections of [18F]MNI-1216 ([18F]ACI-12589).
For each subject participating in the study, the duration of study participation will be up to 78 days.
In Part 1 and Part 2 (if Part 2 is performed), screening assessments will occur within 30 days prior to the Baseline [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit (Day 1). If determined to be necessary by the study team, subjects may participate in an [18F]Florbetapir Imaging Visit up to 6 weeks following Day 1 (will be completed between Day 2 and Day 42). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following each imaging visit performed. In Part 3 (if performed), subjects will participate in a Retest [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit between Day 4 and Day 29 (within 3 days to 4 weeks) following the Baseline [18F]MNI-1216 ([18F]ACI-12589) Imaging Visit (Day 1). A Safety Phone Call for adverse event assessment will occur 4 days (±2 days) following the retest imaging visit, if performed.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study population will be composed of up to 30 subjects, including healthy volunteers and participants with α-synucleinopathies.
| Arm | Type | Receives |
|---|---|---|
| Participants with α-synucleinopathies. | Experimental | Drug: [18F]MNI-1216The study population will be composed of participants with α-synucleinopathies. |
| Healthy volunteers | Active comparator | Drug: [18F]MNI-1216The study population will be composed of health volunteers. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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.
- 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.
Key exclusion criteria (16 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]MNI-1216Also: [18F]ACI-12589[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. | Drug | Healthy volunteers, Participants with α-synucleinopathies. |
Primary outcome
Volume of distribution (VT) of [18F]MNI-1216 across multiple brain regions
Time frame: up to 78 days
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.
Number of participants with [18F]MNI-1216-related adverse events as assessed by CTCAE
Time frame: up to 78 days
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
- Individual participant dataSharing planned: No
Related trials for Alpha-Synucleinopathy
Active, not recruitingObservational study
Quantification of Phosphorylated Alpha-synuclein in Cutaneous Biopsies as a Prospective Biomarker in Parkinson's Disease
REM Behavior Disorder, Parkinson Disease
RecruitingPhase 1
MK-0947 PN-002: An Open-label Study to Evaluate Brain α-synuclein Deposition Using Positron Emission Tomography (PET) and [¹⁸F]MK-0947 in Participants With Parkinson's Disease (PD)
Parkinsons Disease (PD), Healthy Elderly Volunteers
RecruitingPhase 2
An Exploratory Study of the Potential for Rational Immune System Manipulation to Prevent Emergence of Synucleinopathy Manifestations in Persons With REM Sleep Behavior Disorder (RBD)
REM Sleep Behavior Disorder
RecruitingPhase 2
A Study of Donanemab (LY3002813) in Participants With Early Cognitive Decline (TRAILBLAZER-ALZ 7)
Cognitive Dysfunction, Lewy Body Disease
Not yet recruitingPhase 4
Metformin in Parkinson's Disease: Safety and Efficacy
Parkinsons Disease (PD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Russell, MD principal investigator
Invicro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing [18F]MNI-1216 in people with Alpha-Synucleinopathy and Parkinson's Disease, run by Invicro at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume of distribution (VT) of [18F]MNI-1216 across multiple brain regions (time frame: up to 78 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.