Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease
NCT ID: NCT04120493
Last Updated: 2025-10-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
43 participants
INTERVENTIONAL
2019-09-06
2029-12-31
Brief Summary
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Cohort 4 participants will receive high dose AMT-130.
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Detailed Description
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Cohort 1, 2, and 3 evaluated low dose and high dose AMT-130.
Cohort 4 will further evaluate the safety of high dose AMT-130 in participants with low striatal volume. All participants in Cohort 4 will receive high dose AMT-130 and will receive pre- and post-operative dexamethasone.
Cohorts 1 and 2 participants continue follow-up visits through 6 years after receipt of AMT-130. Cohorts 3 and 4 participants continue follow-up visits through 5 years after receipt of AMT-130.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Cohort 1
Low dose rAAV5-miHTT (6x10\^12 gc/subject).
Note: gc = genome copies
intra-striatal rAAV5-miHTT
One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
Cohort 2
High dose rAAV5-miHTT (6x10\^13 gc/subject).
intra-striatal rAAV5-miHTT
One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
Cohorts 1, 2
Imitation (sham) surgery
Imitation (sham) surgery
Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull
Cohort 3
Low dose rAAV5-miHTT (6x10\^12 gc/subject).
High dose rAAV5-miHTT (6x10\^13 gc/subject).
intra-striatal rAAV5-miHTT
One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
Cohort 4
High dose rAAV5-miHTT (6x10\^13 gc/subject).
intra-striatal rAAV5-miHTT
One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
Interventions
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intra-striatal rAAV5-miHTT
One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
Imitation (sham) surgery
Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Participants 25 to 65 years of age of both sexes
* Cohorts 1, 2, \& 4: Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic confidence level (DCL) of 4 OR a DCL of 3 if the subject either meets the definition of multidimensional manifest HD (UHDRS question 80) or has cognitive symptoms
* Cohort 3: Early manifest HD as defined by a UHDRS TFC score of ≥ 11 and EITHER a DCL of 4 or 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 (Movement Disorder Society Task Force criteria).
* HTT gene expansion testing with the presence of ≥40 CAG repeats
* Striatal MRI volume requirements per hemisphere:
* Cohorts 1, 2, \& 3: Putamen ≥2.5 cm\^3 (per side); Caudate ≥2.0 cm\^3 (per side)
* Cohort 4: Putamen \<2.5 cm\^3 (on either side); Caudate \<2.0 cm\^3 (on either 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 (FOCP) 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.
Exclusion Criteria
* Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
* Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or anytime 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 as per local guidelines
* Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder
* Any contraindication to lumbar puncture as per local guidelines
* Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
* 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 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 (ALT) \>2 × upper limit of normal (ULN) b. Aspartate aminotransferase (AST) \>2 × ULN c. Total bilirubin \>2 × ULN d. Alkaline phosphatase (ALP) \>2 × ULN e. Creatinine \>1.5 × ULN f. Platelet count \<100,000/mm3g.Prothrombin time (PT) \>1.2 × ULN h. Partial thromboplastin time (PTT) \>1.2 × ULN
* Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol.
* 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.
* Cohort 4 ONLY: Inability to establish a safe trajectory to administer AMT-130 to the target structures, as assessed by neuroimaging.
25 Years
65 Years
ALL
No
Sponsors
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UniQure Biopharma B.V.
INDUSTRY
Responsible Party
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Principal Investigators
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David H. Margolin, MD, PhD
Role: STUDY_DIRECTOR
uniQure, Inc.
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Arizona (Surgical Site Only)
Tucson, Arizona, United States
University of California, San Francisco
San Francisco, California, United States
CenExel Rocky Mountain Clinical Research
Englewood, Colorado, United States
Rush University Medical Center
Chicago, Illinois, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Michigan Department of Neurology
Ann Arbor, Michigan, United States
Ohio State University
Columbus, Ohio, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
The University of Texas
Houston, Texas, United States
Virginia Commonwealth University VCU School of Medicine, Department of Neurology
Richmond, Virginia, United States
University of Washington Medical Center
Seattle, Washington, United States
Countries
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References
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Pala M, Yilmaz SG. Circular RNAs, miRNAs, and Exosomes: Their Roles and Importance in Amyloid-Beta and Tau Pathologies in Alzheimer's Disease. Neural Plast. 2025 Apr 8;2025:9581369. doi: 10.1155/np/9581369. eCollection 2025.
Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017.
Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006.
Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: April 2020. J Huntingtons Dis. 2020;9(2):185-197. doi: 10.3233/JHD-200002.
Other Identifiers
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CT-AMT-130-01
Identifier Type: -
Identifier Source: org_study_id
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