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Huntington DiseaseEarly Phase 1NCT03810898

iMagemHTT: FIH Evaluation of Novel Mutant Huntingtin PET Radioligands [¹¹C]CHDI-00485180-R and [¹¹C]CHDI-00485626

A Early Phase 1 study testing Radioligand [¹¹C]CHDI-00485180-R and Radioligand [¹¹C]CHDI-00485626 in people with Huntington Disease, run by CHDI Foundation, Inc. at 1 site in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a FIH (first-in-human) adaptive PET (Positron Emission Tomography) imaging study to explore the binding and kinetic properties of two potential mutant huntingtin (mHTT) radioligands; [¹¹C]CHDI-00485180-R and [¹¹C]CHDI-00485626. Read more about this study

Who is it for?
Ages 20 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Huntington Disease
What is being tested?
Radioligand [¹¹C]CHDI-00485180-R and Radioligand [¹¹C]CHDI-00485626
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteBelgium
Study dates
9 Feb 2021to 15 Feb 2023
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 20 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Pre-manifest HDGECs, HDGECs with Stage I HD, HDGECs with Stage II HD and HC participants:
  • Female and male adults, age 20-65 years old, inclusive.
  • Body Mass Index (BMI) between 19 and 35 inclusive.
  • Capacity to give full informed consent in writing, and have read and signed the informed consent form (ICF).
  • Are capable of complying with study procedures, including fasting and blood sampling
  • Able and willing to travel to imaging PET center in Leuven, Belgium.
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  • Willing to comply with the use of adequate contraceptive measures.
  • Pre-manifest HDGECs:
  • Do not have clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score < 4; and
  • Have CAG expansion ≥ 40; and
  • Have a CAP score > 70 (as calculated with CAP formula: AGE * (CAG - 30) / 6.49).
  • HDGECs with Stage I HD:
  • Have clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4; and
  • Have CAG expansion ≥ 40; and
  • Have Stage I HD, defined as UHDRS Total Functional Capacity (TFC) scores between 11 and 13 inclusive.
  • HDGECs with Stage II HD:
  • Have clinical diagnostic motor features of HD, defined as UHDRS Diagnostic Confidence Score = 4; and
  • Have CAG expansion ≥ 40; and Have Stage II HD, defined as UHDRS Total Functional Capacity (TFC) scores between 7 and 10 inclusive.
  • HC participants:
  • Have no known family history of HD; or
  • Have known family history of HD but have been tested for the huntingtin gene glutamine codon (CAG) expansion and are not at genetic risk for HD (CAG < 36).
  • Matched by age +/- 5 years.
  • (Phase 1 only) under 35 years of age.

Who cannot join

  • Pre-manifest HDGECs, HDGECs with Stage I HD, HDGECs with Stage II HD, and HC participants:
  • Currently participating in or less than 30 days after completing participation in other therapeutic or imaging studies.
  • Previous participation in PET imaging study that, cumulatively with the current study, will exceed annual regulatory limits for radiation exposure.
  • 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.
  • Pregnant and breastfeeding females.
  • Concomitant medication (ConMed) use of antiplatelet or anticoagulant therapy (inclusive of acetylsalicylic acid). (See full ConMed list attached.)
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  • Needle phobia.
  • HDGEC participants:
  • If 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:.
  • Family history of HD (unless genetic test confirming negative results).
  • For participants in optional CSF sample collection:
  • Frequent headache, significant lower spinal deformity or major surgery; or
  • Bleeding disorder.

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL

    Leuven, 3000

Other trials in Belgium

About this study

Official title: First-in-Human Adaptive Study to Investigate the Binding and Kinetic Properties of Two Novel PET Ligands and Their Suitability for Quantification of Aggregated Mutant Huntingtin in the Brains of Huntington's Disease Gene-Expansion Carriers

This is a FIH (first-in-human) adaptive PET (Positron Emission Tomography) imaging study to explore the binding and kinetic properties of two potential mutant huntingtin (mHTT) radioligands; [¹¹C]CHDI-00485180-R and [¹¹C]CHDI-00485626.

The binding characteristics of these radioligands will be evaluated first in young (< 35 years of age) healthy control (HC) participants (Phase 1a) and subsequently in young HCs and Huntington's disease gene-expansion carriers (HDGECs) with Stage II HD (Phase 1b). Subsequent phases will continue to explore the radioligands' binding characteristics in HDGECs with Stage II HD (Phase 2a), Stage I HD (Phase 2b) and pre-manifest HDGECs (Phase 2c) and their age matched healthy controls. All phases are cross-sectional and will include comparisons between HCs and HDGECs. Test-retest (TRT) evaluations will be done during Phase 2a, with the option of including further test-retests in Phases 2b, and 2c after review of data by the iMagemHTT Executive Committee. TRT is only applicable to HDGEC participants.

Read more

There are four planned interim analyses at which either radioligand may be dropped if its characteristics are shown to be suboptimal. If successful, the study will establish [¹¹C]CHDI-00485180-R and/or [¹¹C]CHDI-00485626 as fit for further development as drug development tools to measure mHTT levels in HDGECs. This development is intended to demonstrate the value of PET imaging with these radioligands as a disease progression biomarker, predictive biomarker, pharmacodynamic biomarker, and eventually as an efficacy biomarker.

All HDGEC participants will be invited to provide an optional cerebrospinal fluid (CSF) sample that will be collected after the imaging visits are complete. These samples will be processed to evaluate CSF mHTT levels and other potential biomarkers and to explore potential relationships between soluble CSF mHTT levels and mHTT binding identified by [¹¹C]CHDI-00485180-R and/or [¹¹C]CHDI-00485626 PET imaging. Potential CSF biomarkers that might be co-expressed or accumulated in HD may also be examined.

Read the detailed description

The study investigators have developed two novel PET radioligands that will be evaluated for their suitability for use in clinical research settings to quantify mHTT in HDGECs. The PET radioligands do not have any pharmacological effect at the microdoses (total dose <100ug) at which they will be administered; they will not be administered at pharmacological doses. This study has a modular design in two phases, and each phase will enroll a small independent cohort. The execution of each subsequent phase is dependent on results from the previous phase.

Phase 1 is the initial evaluation of the PET radioligands. A suitable PET radioligand is expected to produce quantifiably higher binding in HD participants' brains compared to young HC participants' brains (since they do not express mHTT). Phase 1 is divided in two sub phases: Phase 1a will evaluate the basic safety and kinetic properties as well as brain uptake in three (3) young HCs; Phase 1b will test the difference in binding in six (6) HDGECs with Stage II HD compared to six (6) young HCs (three (3) young HCs will be imaged in addition to the three (3) young HCs from 1a. The rationale behind using young HCs in Phase 1 is to screen out HC participants who may have undiagnosed amyloid-β (Aβ) plaques, a potential off-target binding site for [¹¹C]CHDI-00485180-R. The rationale behind imaging HDGECs with Stage II HD in Phase 1 is based on the hypothesis that the density of mHTT aggregates increases with disease severity, and the ability to detect a difference in binding between HCs and HDGECs is expected to be higher in Stage II HD (more severe stages of HD will not be included in this study). An option to image three (3) pre-manifest HDGECs from Phase 2c (see below) will be included in case the results indicate that brain atrophy (i.e., loss of aggregate due to atrophy) affects the binding and evaluation of the PET radioligands in HDGECs with Stage II HD. For each of the two PET radioligands a Go/ No-Go evaluation will take place (for overview see Figure 1); if satisfactory results are not obtained for a particular radioligand, then that radioligand will not progress to evaluation in further phases. Promising results for either radioligand will lead to that particular radioligand continuing to Phase 2 evaluation.

Phase 2 will evaluate the sensitivity of the PET radioligand(s) to discriminate between different stages and severity of HD. In addition, a TRT in Phase 2 will evaluate the variability of repeated imaging for the PET radioligand. Phase 2 has a sequential design in sub phases that will assess the sensitivity of the radioligand in descending severity of HD: 2a in six (6) HDGECs with Stage II HD and six (6) age-matched controls; 2b in six (6) HDGECs with Stage I HD and six (6) age-matched controls; 2c in six (6) premanifest HDGECs and six (6) age-matched controls. The rationale for imaging groups of descending HD severity is based on the hypothesis that the density of mHTT aggregates increases with disease severity, and the ability to detect a difference in binding between HCs and HDGECs is expected to be lowest in the premanifest stage. This design will enable a stepwise assessment of the sensitivity of the PET radioligands. After each sub-phase a Go/No-Go evaluation will take place; if satisfactory results are not obtained for a particular radioligand then that radioligand will not be evaluated in further sub-phases. Promising results for either radioligand will lead to that particular radioligand continuing to the next sub-phase.

This study design allows each radioligand to be reviewed and analyzed after evaluation in each cohort. The progression through each level of analysis will indicate whether either or both radioligands will measure mHTT aggregate levels with sufficient sensitivity to become potential disease progression and efficacy biomarker(s) in HDGECs.

Being tested
Radioligand [¹¹C]CHDI-00485180-R, Radioligand [¹¹C]CHDI-00485626
Keywords
Huntington Disease, Huntington's Disease, HD, HDGEC, Gene Expansion Carrier, PET, Tracer, Positron Emission Tomography, radioligand, imaging, mHTT, huntingtin, iMagemHTT
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-00485180-RRadiation

    Intravenous injection of radioligand in the arm with PET imaging of the brain.

  • Radioligand [¹¹C]CHDI-00485626Radiation

    Intravenous injection of radioligand in the arm with PET imaging of the brain.

Study groups in NCT03810898
Study groupRoleWhat they receive
Phase 1 (a & b)ExperimentalRadioligand [¹¹C]CHDI-00485180-R and/or Radioligand [¹¹C]CHDI-00485626/ 6 Stage II HDGECs and 6 young (< 35) HCs/ Imaging- MRI and PET/ Both radioligands administered- 1x each/ Optional CSF collection for HDGECs
Receives: Radiation: Radioligand [¹¹C]CHDI-00485180-R; Radiation: Radioligand [¹¹C]CHDI-00485626
Phase 2aExperimentalPer Radioligand- Radioligand [¹¹C]CHDI-00485180-R or Radioligand [¹¹C]CHDI-00485626/ 6 Stage II HDGECs and 6 age matched HCs/ Imaging- MRI and PET/ 1 Radioligand administered 2x (test re-test)- HDGECs/ Optional CSF collection for HDGECs 1 Radioligand administered 1x- HCs/
Receives: Radiation: Radioligand [¹¹C]CHDI-00485180-R; Radiation: Radioligand [¹¹C]CHDI-00485626
Phase 2bExperimentalPer Radioligand- Radioligand [¹¹C]CHDI-00485180-R or Radioligand [¹¹C]CHDI-00485626/ 6 Stage I HDGECs and 6 age matched HCs/ Imaging- MRI and PET/ 1 Radioligand 1 or 2x administered (test re-test optional)- HDGECs/ Optional CSF collection for HDGECs 1 Radioligand administered 1x -HCs/
Receives: Radiation: Radioligand [¹¹C]CHDI-00485180-R; Radiation: Radioligand [¹¹C]CHDI-00485626
Phase 2cExperimentalPer Radioligand- Radioligand [¹¹C]CHDI-00485180-R or Radioligand [¹¹C]CHDI-00485626/ 6 Pre-manifest HDGECs and 6 age matched HCs/ Imaging- MRI and PET/ 1 Radioligand administered 1 or 2x (test re-test optional)- HDGECs/ Optional CSF collection for HDGECs 1 Radioligand administered 1x- HCs/
Receives: Radiation: Radioligand [¹¹C]CHDI-00485180-R; Radiation: Radioligand [¹¹C]CHDI-00485626

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The VT (volume of distribution total) of 2 discrete PET markers will be measured with PET imaging.

    VT (volume of distribution total) is derived from the data collected during each PET scan. VT is the amount of the PET marker in a volume of tissue (i.e., a concentration).

    Measured: 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.

  1. First posted22 Jan 2019
  2. Study start9 Feb 2021
  3. Primary completion15 Feb 2023
  4. Study completion15 Feb 2023

Why it stopped: Study terminated per protocol design post interim analysis review after Phase 2a. No SAEs or safety issues were noted.

Resources

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
Huntington's disease gene expansion carriers (HDGEC) compared to healthy controls (HC)
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03810898
Sponsor's protocol ID
C-000418-2
Status last verified
May 2023
First submitted
7 Dec 2018
Last updated
6 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Delva A, Koole M, Serdons K, Bormans G, Skinbjerg M, Khetarpal V, Liu L, Bard J, Doot R, Warner JH, Sathe S, Sampaio C, Wood A, Van Laere K, Vandenberghe W. PET imaging with [(1)(1)C]CHDI-00485180-R, designed as radioligand for aggregated mutant huntingtin, in people with Huntington's disease. Eur J Nucl Med Mol Imaging. 2025 Nov;52(13):5124-5134. doi: 10.1007/s00259-025-07394-w. Epub 2025 Jun 18.

    PubMed 40527969

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Radioligand [¹¹C]CHDI-00485180-R and Radioligand [¹¹C]CHDI-00485626 in people with Huntington Disease, 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 23 inclusion and 14 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: stopped early, as of the sponsor's last update on 6 May 2023. 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?

The study was stopped early (reason given: Study terminated per protocol design post interim analysis review after Phase 2a. No SAEs or safety issues were noted.). Results are not available in the source record.

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?

The VT (volume of distribution total) of 2 discrete PET markers will be measured with PET imaging. (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?

On the ClinicalTrials.gov record for NCT03810898, which also lists 1 linked publication.

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 6 May 2023.

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