Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington Disease
- Conditions
- Huntington’s DiseaseMedDRA version: 20.0Level: PTClassification code: 10070668Term: Huntington's disease Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2024-511766-37-00
- Lead Sponsor
- uniQure biopharma B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 15
Able and willing to provide written informed consent prior to the study and any study-related procedure., Male and female participants 25 to 65 years of age., Cohorts 1 & 2: Early manifest HD as defined by a UHDRS TFC score of 9 to 13 and EITHER a. a DCL of 4 OR b. a DCL of 3 with either a positive (Yes) response to UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria). Cohort 3: Early manifest HD as defined by a UHDRS TFC score of =11 and EITHER a. a DCL of 4 OR b. a DCL of 3 with either a positive (Yes) response to UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder (American Psychiatric Association, 2013; MDS Task Force criteria)., HTT gene expansion testing with the presence of =40 CAG repeats., Striatal MRI volume requirements per hemisphere: a. Putamen =2.5 cm3 (per side) b. Caudate =2.0 cm3 (per side), All HD concomitant medications (addressing motor, behavioral, and cognitive symptoms) must be stable for 3 months prior to Screening with no change in clinical symptoms requiring change in medication prior to anticipated administration procedure., Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol., All female participants of childbearing potential (FOCPs) must have a negative serum pregnancy test at Screening (and Visit 1A, as appropriate), a negative pregnancy urine dipstick at Baseline, and not be breastfeeding. All FOCPs and sexually mature males must be compliant with a highly effective birth control method.
Evidence of suicide risk, defined as: a. Suicide attempt within 1 year prior to Screening (Visit 1/1A). b. Suicidal ideation as defined by a positive response to question 5 on the C-SSRS Suicidal Ideation Section within 60 days prior to Screening (Visit 1/1A). c. Significant risk of suicide as judged by the Investigator., Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study., Current or recurrent disease (including pre-existing cardiovascular or pulmonary conditions), infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a participant’s safety or their ability to undergo the neurosurgical procedure (10+ hour surgical procedure) or comply with the procedures and study visit schedule., Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients., Any known allergy to gadoteridol (ProHance®)., Screening laboratory values (as measured by the central laboratory): a. Alanine aminotransferase >2 × upper limit of normal (ULN) b. Aspartate aminotransferase >2 × ULN c. Total bilirubin >2 × ULN d. Alkaline phosphatase >2 × ULN e. Creatinine >1.5 × ULN f. Platelet count <100,000/mm3 g. Prothrombin time >1.2 × ULN h. Partial thromboplastin time >1.2 × ULN, Additional Exclusion Criteria for Participants in Cohort 3: Known immunocompromised status including participants who have undergone organ transplantation or who test positive at Screening for the human immunodeficiency virus (HIV); or who are at risk of pathogen reactivation if immunosuppressed, including participants who test positive at screening for hepatitis C virus antibody (anti-HCV), hepatitis C virus ribonucleic acid (HCV RNA), hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc); or who have history of active tuberculosis or a positive tuberculosis blood test during screening. For participants with an indeterminate tuberculosis blood test result or positive tuberculosis test result, repeat testing is recommended., Additional Exclusion Criteria for Participants in Cohort 3: Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol., Additional Exclusion Criteria for Participants in Cohort 3: Any participant with an active infection (e.g., coronavirus disease 2019 [COVID-19]) at Screening or at the time of treatment that requires medical intervention. Participants may rescreen, or if screened eligible and an open surgical slot is available, may receive treatment after recovery., Receipt of an experimental agent within 60 days or 5 half-lives prior to Screening or any time over the duration of this study., Participation in an investigational study or investigational paradigm (e.g., exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or any time over the duration of this study., Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter., Any history of gene therapy, RNA, or DNA targeted HD-specific investigational agents, such as antisense oligonucleotides (ASOs), cell transplantation, or any other experimental brain surgery., Any contraindication to 3.0 Tesla MRI scans or lumbar punctures as per local guidelines., Brain and
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method