iMagemHTT-009- FIH Evaluation of Novel Mutant Huntingtin PET Radioligand [11C]CHDI-00491009

NCT06634628 | Recruiting Early Phase 1

• 1 other identifier: CS-5583
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Huntington Disease; HD; PET Tracer; Huntington's; Huntington's Disease; Positron Emission Tomography; Radioligand; Imaging; mHTT

Keywords

iMagemHTT; Huntington Disease; HD; PET Tracer; Positron Emission Tomography; radioligand; imaging; mHTT; huntingtin; Huntington's Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Time Frame: Single point measure - 90 minutes scan

Study Arms (3)

Cohort 1

EXPERIMENTAL

Radioligand \[11C\]CHDI-00491009 3 HCs - MRI and PET Radioligand is administered 1x each person

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

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.)

Radiation: Radioligand [11C]CHDI-00491009

Interventions

Radioligand [11C]CHDI-00491009 RADIATION

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

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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:
• \. 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.
• \. 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:

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• CHDI Foundation, Inc.: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (1)

Universitaire Ziekenhuizen Leuven/ UZ Leuven/ UZL

Leuven, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Wim Vandenberghe, MD, PhD

CONTACT

+32 16344280; wim.vandenberghe@uzleuven.be

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: People with Huntington's disease (PwHD) compared to healthy controls (HC)

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 10, 2024
• Study Start: February 24, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

BE (1)