Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06634628
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-08
Brief Title:
iMagemHTT- 009- FIH Evaluation of Novel Mutant Huntingtin PET Radioligand 11CCHDI-00491009
Sponsor:
None
Organization:
None
Study Overview
Official Title:
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 the Brains of People With Huntingtons Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
iMagemHTT-009
Brief Summary:
This is a FIH first-in-human study to evaluate the clinical utility of the radioligand 11CCHDI-00491009 as a PET tracer that binds specifically to mutant huntingtin mHTT aggregates in Huntingtons disease HD
The study is divided into three cohorts defined by the Huntingtons 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
The study is divided into three cohorts defined by the Huntingtons 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 11CCHDI-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 05 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 gono-go decision will be made if 11CCHDI-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 11CCHDI-00491009 is a suitable radioligand to measure mHTT aggregate levels with sufficient sensitivity to become a potential disease progression and efficacy biomarker in Huntingtons disease
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 gono-go decision will be made if 11CCHDI-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 11CCHDI-00491009 is a suitable radioligand to measure mHTT aggregate levels with sufficient sensitivity to become a potential disease progression and efficacy biomarker in Huntingtons disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None