Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington Disease


This is the first study of AMT-130 in patients with early manifest HD and is designed to establish safety and proof-of-concept (PoC). CT-AMT-130-01 is a Phase I/II, randomized, multicenter, dose escalation, double-blind, imitation surgery, first-in-human (FIH) study.


  • Huntington Disease


Eligible Ages
Between 25 Years and 65 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic classification 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 - HTT gene expansion testing with the presence of ≥40 CAG repeats. - Striatal MRI volume requirements per hemisphere: Putamen ≥2.5 cm3 (per side); Caudate ≥2.0 cm3 (per side) - All HD concomitant medications (addressing motor, behavioral, and cognitive symptoms) stable for 3 months prior to Screening. - Able and willing to provide written informed consent - Able and willing to comply with all procedures and study visits

Exclusion Criteria

  • Evidence of suicide risk - 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, etc.) 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 (ASO), cell transplantation or any other experimental brain surgery. - Any contraindication to lumbar puncture or 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. - 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, infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule

Study Design

Phase 1/Phase 2
Study Type
Intervention Model
Sequential Assignment
Primary Purpose
Triple (Participant, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Cohort 1
Low dose rAAV5-miHTT (6x10^12 gc/subject).
  • Genetic: intra-striatal rAAV5-miHTT
    One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
    Other names:
    • AMT-130
Cohort 2
High dose rAAV5-miHTT (6x10^13 gc/subject).
  • Genetic: intra-striatal rAAV5-miHTT
    One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain
    Other names:
    • AMT-130
Sham Comparator
Cohorts 1 and 2
Imitation (sham) surgery
  • Other: Imitation (sham) surgery
    Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Danielle Buchanan

More Details

UniQure Biopharma B.V.

Study Contact

Diane Lopez, MS

Detailed Description

AMT-130 is an investigational, single administration gene therapy intended to modify the disease course for HD. Preclinical studies have shown that AMT-130 lowers huntingtin protein and is associated with decreased progression of Huntington disease signs in animal models. This 5-year trial consists of a blinded 12-month Core Study Period to evaluate the safety and potential impact of AMT-130 on disease progression and an unblinded 4-year Long-Term Period with periodic follow-up visits to evaluate the safety of AMT-130 and disease progression in treated individuals. Following completion of the 12-month blinded post treatment follow-up period, subjects will be individually unblinded. Once the crossover has been activated after review of data by the DSMB and FDA, subjects randomized to the imitation (sham) procedure who continue to meet inclusion/exclusion criteria (including adequate MRI striatal volumes) will be allowed to crossover to receive AMT-130 treatment.