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
- 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.
- 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.
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Intrastriatal administration of low dose rAAV5-miHTT (6E12 gc/subject). Single dose administration.||
|Intrastriatal administration of high dose rAAV5-miHTT (6E13 gc/subject). Single dose administration.||
|Imitation surgery patients randomized across both Cohort 1 and 2||
- UniQure Biopharma B.V.
Study ContactDavid Cooper, MD, MBA
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.