New PET tracer ([11C]CHDI-00491009) to image mutant huntingtin in Huntington disease
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 project will test a new PET tracer ([11C]CHDI-00491009) to see if it binds mutant huntingtin aggregates in adults with Huntington disease and in healthy volunteers.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 27 (estimated) |
| Ages | 18 Years to 64 Years |
| Sex | All |
| Sponsor | CHDI Foundation, Inc. Academic / other |
| Drugs / interventions | radiation |
| Locations | 1 site (Leuven) |
| Trial ID | NCT06634628 on ClinicalTrials.gov |
What this trial studies
This first-in-human, adaptive early-phase study administers microdoses (<0.5 μg) of the PET radioligand [11C]CHDI-00491009 to adults with genetically confirmed Huntington disease and to matched healthy controls to determine tracer kinetics and target binding. Enrollment is in three sequential cohorts defined by HD-ISS stages, with interim analyses after each cohort and a test-retest arm to measure reproducibility. Exploratory blood biomarkers including soluble mutant huntingtin, total huntingtin, and a somatic instability index will be collected to relate imaging signal to molecular measures. The study aims to establish whether the tracer yields quantifiable, stage-sensitive signal and to define optimal quantification methods for future clinical research.
Who should consider this trial
Good fit: Adults aged 18–64 with BMI 19–35 who can give informed consent and travel to Leuven are eligible, specifically healthy volunteers and people with genetically confirmed HD in HD-ISS Stage 2 or 3 who meet the listed CAG and PIN criteria and can comply with PET and blood procedures.
Not a fit: People outside the 18–64 age or BMI ranges, those who cannot travel to Leuven or comply with fasting and blood draws, pregnant individuals, or people with HD outside Stage 2–3 are unlikely to qualify or receive benefit from this protocol.
Why it matters
Potential benefit: If successful, the tracer could provide a noninvasive imaging biomarker to measure mutant huntingtin in the brain and help track disease progression or treatment effects.
How similar studies have performed: Preclinical work supports this ligand, but there are few if any widely validated mutant-huntingtin PET tracers in humans, making this a novel first-in-human evaluation.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
PwHD HD-ISS Stages 2 and 3 and HC participants who:
1. Are female or male adults, age 18-64 years old, inclusive.
2. Have body mass index (BMI) between 19 and 35, inclusive.
3. Have capacity to give full informed consent in writing and have read and signed the informed consent form (ICF).
4. Are able to comply with study procedures, including fasting and blood sampling.
5. Are able and willing to travel to the imaging center in Leuven, Belgium.
6. Are willing to comply with the use of adequate contraceptive measures.
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 \[prognostic index normed for HD (PIN) where PIN = (PIHD - 883)/1044 where PIHD = 51 x TMS + (-34) x SDMT + 7 x Age x (CAG - 34) (TMS is the UHDRS Total Motor Score, and SDMT is the UHDRS Symbol Digit Modalities Test)\].
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).
Exclusion Criteria:
PwHD HD-ISS Stages 2 and 3 and HC participants who:
1. Are currently participating in, or are less than 30 days after completing participation in, other therapeutic or imaging studies.
2. 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.
3. 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.
4. Are pregnant and breastfeeding females.
5. Have concomitant use of antiplatelet or anticoagulant therapy (inclusive of acetylsalicylic acid).
6. Have a bleeding disorder.
7. Have a needle phobia.
8. Have any metal objects present in the body that are incompatible with MRI.
9. Have metal objects present in the body that are compatible with MRI and are located in the head or neck.
10. 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:
11. 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:
12. Have a family history of HD and have not been tested for the huntingtin gene (CAG) expansion.
Where this trial is running
Leuven
- Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL — Leuven, Belgium (Recruiting)
Study contacts
- Study coordinator: Wim Vandenberghe, MD, PhD
- Email: wim.vandenberghe@uzleuven.be
- Phone: +32 16344280
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.