Huntington DiseaseEarly Phase 1iMagemHTT-009NCT06634628
iMagemHTT-009- FIH Evaluation of Novel Mutant Huntingtin PET Radioligand [11C]CHDI-00491009
A Early Phase 1 study testing Radioligand [11C]CHDI-00491009 in people with Huntington Disease and HD, run by CHDI Foundation, Inc. at 1 site in Belgium.
Trial summary
This is a FIH (first-in-human) study to evaluate the clinical utility of the radioligand [11C]CHDI-00491009 as a PET tracer that binds specifically to mutant huntingtin (mHTT) aggregates in Huntington's disease (HD). Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Huntington Disease, HD, PET Tracer
- What is being tested?
- Radioligand [11C]CHDI-00491009
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteBelgium
- Study dates
- 24 Feb 2026to Mar 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- PwHD HD-ISS Stages 2 and 3 and HC participants who:
- Are female or male adults, age 18-64 years old, inclusive.
- Have body mass index (BMI) between 19 and 35, inclusive.
- Have capacity to give full informed consent in writing and have read and signed the informed consent form (ICF).
- Are able to comply with study procedures, including fasting and blood sampling.
- Are able and willing to travel to the imaging center in Leuven, Belgium.
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- Are willing to comply with the use of adequate contraceptive measures.
- HD-ISS Stage 2 participants who:
- Have a huntingtin gene CAG expansion between 40 and 50, inclusive; and
- Are classified within HD-ISS Stage 2 per the HD-ISS criteria using HD-ISS Modified Stage calculator.
- Have a PIN score of 0.47 to 1.84 [prognostic index normed for HD (PIN) where PIN = (PIHD - 883)/1044 where PIHD = 51 x TMS + (-34) x SDMT + 7 x Age x (CAG - 34) (TMS is the UHDRS Total Motor Score, and SDMT is the UHDRS Symbol Digit Modalities Test)].
- HD-ISS Stage 2 participants who:
- 7. Have a huntingtin gene CAG expansion between 40 and 50, inclusive; and 8. Are classified within HD-ISS Stage 2 per the HD-ISS criteria using HD-ISS Modified Stage calculator.
- 9. Have a PIN score of 0.47 to 1.84 [prognostic index normed for HD (PIN) where PIN = (PIHD - 883)/1044 where PIHD = 51 x TMS + (-34) x SDMT + 7 x Age x (CAG - 34) (TMS is the UHDRS Total Motor Score, and SDMT is the UHDRS Symbol Digit Modalities Test)].
- HC participants who:
- 13. Have no known family history of HD; or 14. Have a known family history of HD and have been tested for the huntingtin gene CAG expansion and are not at genetic risk for HD (CAG < 36).
- 15. Age match (+/- 5 years) and biological sex match to each HD participant in Cohort 2 and Cohort 3 (except for Cohort 1, no matching).
Who cannot join
- PwHD HD-ISS Stages 2 and 3 and HC participants who:
- Are currently participating in, or are less than 30 days after completing participation in, other therapeutic or imaging studies.
- Have previously participated in a PET imaging study in the past 12 months that, cumulatively with the current study, will exceed annual regulatory limits for radiation exposure.
- Have any disease, condition, or concomitant medication that significantly compromises the function of the body systems and that, in the opinion of the Investigator, might interfere with the conduct of the study or its interpretation.
- Are pregnant and breastfeeding females.
- Have concomitant use of antiplatelet or anticoagulant therapy (inclusive of acetylsalicylic acid).
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- Have a bleeding disorder.
- Have a needle phobia.
- Have any metal objects present in the body that are incompatible with MRI.
- Have metal objects present in the body that are compatible with MRI and are located in the head or neck.
- Have any clinically significant results on safety laboratory tests that, in the opinion of the Investigator, would either put the participant at risk or interfere with the conduct of the study or interpretation of data. These tests include, but are not limited to:
- a. positive results for HBsAg, HepC, HIV-1 or HIV-2 (will also be reported as required by local/national regulations),
- b. clinically significant, abnormal results for safety laboratory tests.
- PwHD participants who:
- If they are using any antidepressant, psychoactive, psychotropic or other medications or nutraceuticals used to treat HD, the use of inappropriate (e.g., non-therapeutically high) or unstable dose within 30 days prior to participation.
- HC participants who:
- Have a family history of HD and have not been tested for the huntingtin gene (CAG) expansion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL
Leuven, 3000
Wim Vandenberghe, MD, PhD, wim.vandenberghe@uzleuven.be
Koen Van Laere, MD, PhD, DSc, + 3216343711, koen.vanlaere@uzleuven.be
About this study
Official title: First in Human Adaptive Study to Investigate the Kinetic Properties of the Novel PET Radioligand [11C]CHDI-00491009 and Its Suitability for Quantification of Aggregated Mutant Huntingtin in the Brains of People With Huntington's Disease
This is a FIH (first-in-human) study to evaluate the clinical utility of the radioligand [11C]CHDI-00491009 as a PET tracer that binds specifically to mutant huntingtin (mHTT) aggregates in Huntington's disease (HD).
The study is divided into three cohorts defined by the Huntington's Disease Integrated Staging System (HD-ISS): Cohort 1 - initial tracer validation (3 healthy controls (HCs)); Cohort 2 - target validation and test-retest variability (6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs); Cohort 3 - target sensitivity (6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs). An interim analysis (IA) will be conducted after the completion of each cohort, followed by a final analysis for the study.
In addition to imaging, exploratory biomarkers, including somatic instability index, soluble mHTT and total huntingtin (HTT), will be assessed. All participants with HD (PwHD) will have an additional blood sample drawn at the screening visit to assess the somatic instability index and will also be invited to provide an optional cerebrospinal fluid (CSF) sample for measurement of soluble mHTT and total HTT.
Read the detailed description
The PET radioligand [11C]CHDI-00491009 will be evaluated for its suitability for use in clinical research to quantify mHTT aggregates in PwHD. The PET radioligand is administered as a microdose of <0.5 μg and will not be administered at pharmacological doses. This study has an adaptive and modular design with three consecutive cohorts. The execution of each cohort is dependent on results from the previous cohort.
Cohort 1- Screening and imaging of 3 HCs followed by an interim analysis to evaluate the tracer kinetics without target expression (mHTT) to identify potential brain penetrating radiometabolites or other issues that may interfere with accurate quantification. If the kinetics are found to be favorable during the IA and there are no other confounding issues that may interfere with accurate quantification, then the study will proceed to target validation with Cohort 2.
Cohort 2- Screening and imaging of 6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs. 3 HCs and 3 HD participants from Cohort 2 will be imaged twice to determine variability between scans (test-retest; TRT). An IA will be conducted after completion of Cohort 2 that will establish the optimal method for quantification of signal and endpoint, as well as evaluating the tracer binding in HD compared to HC participants and determining the TRT reproducibility. Results will then be reviewed and a go/no-go decision will be made; if [11C]CHDI-00491009 demonstrates favorable kinetic and binding properties and go criteria are met, the study will proceed to Cohort 3 evaluation. Otherwise, the study will be terminated.
Cohort 3- Screening and imaging of 6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs. An IA will be conducted after completion of Cohort 3 to evaluate binding in HD compared to HC participants.
This adaptive study design allows for review and analysis after each cohort. The progression through each level of analysis will indicate whether [11C]CHDI-00491009 is a suitable radioligand to measure mHTT aggregate levels with sufficient sensitivity to become a potential disease progression and efficacy biomarker in Huntington's disease.
- Conditions
- Huntington Disease, HD, PET Tracer, Positron Emission Tomography, Radioligand, Imaging
- Being tested
- Radioligand [11C]CHDI-00491009
- Keywords
- iMagemHTT, Huntington Disease, HD, PET Tracer, Positron Emission Tomography, radioligand, imaging, mHTT, huntingtin, Huntington's Disease
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radioligand [11C]CHDI-00491009Radiation
Intravenous injection of radioligand in the arm with PET imaging of the brain.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Radioligand [11C]CHDI-00491009 3 HCs - MRI and PET Radioligand is administered 1x each person Receives: Radiation: Radioligand [11C]CHDI-00491009 |
| Cohort 2 | Experimental | Radioligand [11C]CHDI-00491009 6 HCs - MRI and PET 6 PwHD HD-ISS Stage 2 - MRI and PET Radioligand administered 2x (TRT) for 3 HCs and 3 PwHD Radioligand administered 1x for 3 HCs and 3 PwHD In addition, optional CSF collection for all PwHD Receives: Radiation: Radioligand [11C]CHDI-00491009 |
| Cohort 3 | Experimental | Radioligand [11C]CHDI-00491009 6 HCs - MRI and PET 6 PwHD HD-ISS Stage 3 - MRI and PET Radioligand administered 1x for 6 HCs and 6 PwHD In addition, optional CSF collection for all PwHD Depending on previous results and as decided by executive committee, TRT may be included in Cohort 3. A TRT decision would include one extra imaging session per participant (i.e., radioligand administered 2x per participant.) Receives: Radiation: Radioligand [11C]CHDI-00491009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The VT (volume of distribution total) of the PET radioligand will be measured with PET imaging.
The VT (volume of distribution total) of the PET radioligand will be measured with PET imaging. [Time Frame: Single point measure - 90 minutes scan] VT is derived from the data collected during each PET scan.
Measured: Time Frame: Single point measure - 90 minutes scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2024
- Study start24 Feb 2026
- Primary completionMar 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington DiseaseStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- People with Huntington's disease (PwHD) compared to healthy controls (HC)
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CHDI Foundation, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06634628
- Sponsor's protocol ID
- CS-5583
- Acronym
- iMagemHTT-009
- Status last verified
- Mar 2026
- First submitted
- 8 Oct 2024
- Last updated
- 13 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First in Human Adaptive Study to Investigate the Kinetic Properties of the Novel PET Radioligand [11C]CHDI-00491009 and Its Suitability for Quantification of Aggregated Mutant Huntingtin in the Brains of People With Huntington's Disease
- ClinicalTrials.gov ID
- NCT06634628
- Acronym / sponsor ID
- iMagemHTT-009 / CS-5583
- Conditions
- Huntington Disease, HD, PET Tracer, Positron Emission Tomography, Radioligand, Imaging
- Keywords
- iMagemHTT, Huntington Disease, HD, PET Tracer, Positron Emission Tomography, radioligand, imaging, mHTT
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- CHDI Foundation, Inc.University, hospital or other
- Collaborators
- Universitaire Ziekenhuizen KU Leuven
- Study start
- 24 Feb 2026 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 10 Oct 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.
This is a FIH (first-in-human) study to evaluate the clinical utility of the radioligand [11C]CHDI-00491009 as a PET tracer that binds specifically to mutant huntingtin (mHTT) aggregates in Huntington's disease (HD).
The study is divided into three cohorts defined by the Huntington's Disease Integrated Staging System (HD-ISS): Cohort 1 - initial tracer validation (3 healthy controls (HCs)); Cohort 2 - target validation and test-retest variability (6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs); Cohort 3 - target sensitivity (6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs). An interim analysis (IA) will be conducted after the completion of each cohort, followed by a final analysis for the study.
In addition to imaging, exploratory biomarkers, including somatic instability index, soluble mHTT and total huntingtin (HTT), will be assessed. All participants with HD (PwHD) will have an additional blood sample drawn at the screening visit to assess the somatic instability index and will also be invited to provide an optional cerebrospinal fluid (CSF) sample for measurement of soluble mHTT and total HTT.
Detailed description
The PET radioligand [11C]CHDI-00491009 will be evaluated for its suitability for use in clinical research to quantify mHTT aggregates in PwHD. The PET radioligand is administered as a microdose of <0.5 μg and will not be administered at pharmacological doses. This study has an adaptive and modular design with three consecutive cohorts. The execution of each cohort is dependent on results from the previous cohort.
Cohort 1- Screening and imaging of 3 HCs followed by an interim analysis to evaluate the tracer kinetics without target expression (mHTT) to identify potential brain penetrating radiometabolites or other issues that may interfere with accurate quantification. If the kinetics are found to be favorable during the IA and there are no other confounding issues that may interfere with accurate quantification, then the study will proceed to target validation with Cohort 2.
Cohort 2- Screening and imaging of 6 HD-ISS Stage 3 participants and 6 age and biological sex-matched HCs. 3 HCs and 3 HD participants from Cohort 2 will be imaged twice to determine variability between scans (test-retest; TRT). An IA will be conducted after completion of Cohort 2 that will establish the optimal method for quantification of signal and endpoint, as well as evaluating the tracer binding in HD compared to HC participants and determining the TRT reproducibility. Results will then be reviewed and a go/no-go decision will be made; if [11C]CHDI-00491009 demonstrates favorable kinetic and binding properties and go criteria are met, the study will proceed to Cohort 3 evaluation. Otherwise, the study will be terminated.
Cohort 3- Screening and imaging of 6 HD-ISS Stage 2 participants and 6 age and biological sex-matched HCs. An IA will be conducted after completion of Cohort 3 to evaluate binding in HD compared to HC participants.
This adaptive study design allows for review and analysis after each cohort. The progression through each level of analysis will indicate whether [11C]CHDI-00491009 is a suitable radioligand to measure mHTT aggregate levels with sufficient sensitivity to become a potential disease progression and efficacy biomarker in Huntington's disease.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- People with Huntington's disease (PwHD) compared to healthy controls (HC)
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Radiation: Radioligand [11C]CHDI-00491009Radioligand [11C]CHDI-00491009 3 HCs - MRI and PET Radioligand is administered 1x each person |
| Cohort 2 | Experimental | Radiation: Radioligand [11C]CHDI-00491009Radioligand [11C]CHDI-00491009 6 HCs - MRI and PET 6 PwHD HD-ISS Stage 2 - MRI and PET Radioligand administered 2x (TRT) for 3 HCs and 3 PwHD Radioligand administered 1x for 3 HCs and 3 PwHD In addition, optional CSF collection for all PwHD |
| Cohort 3 | Experimental | Radiation: Radioligand [11C]CHDI-00491009Radioligand [11C]CHDI-00491009 6 HCs - MRI and PET 6 PwHD HD-ISS Stage 3 - MRI and PET Radioligand administered 1x for 6 HCs and 6 PwHD In addition, optional CSF collection for all PwHD Depending on previous results and as decided by executive committee, TRT may be included in Cohort 3. A TRT decision would include one extra imaging session per participant (i.e., radioligand administered 2x per participant.) |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (17 listed)
- Are female or male adults, age 18-64 years old, inclusive.
- Have body mass index (BMI) between 19 and 35, inclusive.
- Have capacity to give full informed consent in writing and have read and signed the informed consent form (ICF).
- Are able to comply with study procedures, including fasting and blood sampling.
- Are able and willing to travel to the imaging center in Leuven, Belgium.
Key exclusion criteria (17 listed)
- Are currently participating in, or are less than 30 days after completing participation in, other therapeutic or imaging studies.
- Have previously participated in a PET imaging study in the past 12 months that, cumulatively with the current study, will exceed annual regulatory limits for radiation exposure.
- Have any disease, condition, or concomitant medication that significantly compromises the function of the body systems and that, in the opinion of the Investigator, might interfere with the conduct of the study or its interpretation.
- Are pregnant and breastfeeding females.
- Have concomitant use of antiplatelet or anticoagulant therapy (inclusive of acetylsalicylic acid).
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 |
|---|---|---|
| Radioligand [11C]CHDI-00491009Intravenous injection of radioligand in the arm with PET imaging of the brain. | Radiation | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
The VT (volume of distribution total) of the PET radioligand will be measured with PET imaging.
Time frame: Time Frame: Single point measure - 90 minutes scan
The VT (volume of distribution total) of the PET radioligand will be measured with PET imaging. [Time Frame: Single point measure - 90 minutes scan] VT is derived from the data collected during each PET scan.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2026.
- Individual participant dataSharing planned: Undecided
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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.
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 Radioligand [11C]CHDI-00491009 in people with Huntington Disease and HD, run by CHDI Foundation, Inc. at 1 site in Belgium.
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 17 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 13 Mar 2026. 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 Belgium. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wim Vandenberghe, MD, PhD (+32 16344280, wim.vandenberghe@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The VT (volume of distribution total) of the PET radioligand will be measured with PET imaging. (time frame: Time Frame: Single point measure - 90 minutes scan). 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 13 Mar 2026.