Purpose

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.

Condition

Eligibility

Eligible Ages
Between 25 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • First 4 subjects in Cohort 1: early manifest HD (Stage 2). All remaining subjects in Cohort 1 and all subjects in Cohort 2: early manifest HD (Stages 1 and 2).
  • HTT gene expansion testing with the presence of ≥44 CAG repeats.
  • Striatal MRI volume requirements per hemisphere: Putamen ≥2.5 cm3 (per side); Caudate ≥2.0 cm3 (per side)
  • All HD concomitant medications stable for 3 months prior to Screening.

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, etc.) within 60 days prior to Screening or anytime over the duration of this study.
  • Presence of an implanted deep brain stimulation device.
  • 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 CSF homeostasis and circulation, increased intracranial pressure (including presence of a shunt for the drainage of CSF or an implanted CNS catheter), malformations and/or tumors.
  • Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
  • Current use of medications that could improve or worsen chorea or other HD movements including typical neuroleptics, tetrabenazine and deutetrabenazine.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1
Intrastriatal administration of low dose rAAV5-miHTT (6E12 gc/subject). Single dose administration.
  • Genetic: rAAV5-miHTT
    Single dose administration of rAAV5-miHTT gene therapy
    Other names:
    • AMT-130
Experimental
Cohort 2
Intrastriatal administration of high dose rAAV5-miHTT (6E13 gc/subject). Single dose administration.
  • Genetic: rAAV5-miHTT
    Single dose administration of rAAV5-miHTT gene therapy
    Other names:
    • AMT-130
Sham Comparator
Imitation Surgery
Imitation surgery patients randomized across both Cohort 1 and 2
  • Procedure: Imitation surgery
    Bilateral partial thickness burr holes placed, no intrastriatal injections

Recruiting Locations

The University of Texas
Houston, Texas 77030
Contact:
Jamie Sims
713-500-7763
Jamie.Sims@uth.tmc.edu

More Details

NCT ID
NCT04120493
Status
Recruiting
Sponsor
UniQure Biopharma B.V.

Study Contact

David Cooper, MD, MBA
339-970-7081
amt130_clinical_trials@uniqure.com

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 improved Huntington disease signs in animal models.

This 5-year trial consists of a blinded 18-month Core Study Period to evaluate the safety and potential impact of AMT-130 on disease progression and an unblinded 3.5-year Long-Term Period with annual follow-up visits to evaluate the safety of AMT-130 and disease progression.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.