Trials / Recruiting

RecruitingNCT06634628

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

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

Status: Recruiting
Phase: EARLY_Phase 1
Study type: Interventional
Enrollment: 27 (estimated)

Sponsor: CHDI Foundation, Inc. · Academic / Other
Sex: All
Age: 18 Years – 64 Years
Healthy volunteers: Accepted

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.

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

Interventions

Type	Name	Description
RADIATION	Radioligand [11C]CHDI-00491009	Intravenous injection of radioligand in the arm with PET imaging of the brain.

Timeline

Start date: 2026-02-24
Primary completion: 2028-03-01
Completion: 2028-03-01
First posted: 2024-10-10
Last updated: 2026-03-13

Locations

1 site across 1 country: Belgium

Source: ClinicalTrials.gov record NCT06634628. Inclusion in this directory is not an endorsement.