First in Human Adaptive Study to Investigate the Kinetic Properties of the Novel PET Radioligand 11CCHDI-00491009 and Its Suitability for Quantification of Aggregated Mutant Huntingtin in People With Huntingtons Disease

What this Trial Is About

Researchers are evaluating a new PET radioligand called 11CCHDI-00491009 to see if it can specifically bind to mutant huntingtin mHTT aggregates in the brains of people with Huntingtons disease HD. This first-in-human study uses an adaptive design with three groups based on Huntingtons Disease Integrated Staging System HD-ISS stages, including healthy controls and participants with different HD stages. The study also explores biomarkers like somatic instability index and soluble mHTT to better understand the disease. The study involves three cohorts Cohort 1 includes 3 healthy controls receiving one PET imaging session to validate tracer kinetics without mHTT target. Cohort 2 includes 6 HD-ISS Stage 3 participants and 6 matched healthy controls with PET imaging and MRI some participants have repeat scans to assess variability. Cohort 3 includes 6 HD-ISS Stage 2 participants and 6 matched controls with similar imaging and optional cerebrospinal fluid sampling. Each cohorts results guide progression to the next, allowing detailed evaluation of the radioligands suitability. Participants undergo PET imaging with a microdose injection of the radioligand lasting about 90 minutes per scan, along with MRI scans. Blood samples are collected at screening to assess biomarkers, and participants with HD may provide optional cerebrospinal fluid samples. The main measure is the radioligands volume of distribution in the brain. Safety lab tests and clinical evaluations are done to monitor participant health throughout the study, which is designed to determine if the radioligand can be used as a biomarker for disease progression.

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