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Trial record 4 of 31 for:    Recruiting Studies | Huntington Disease

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

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ClinicalTrials.gov Identifier: NCT04120493
Recruitment Status : Recruiting
First Posted : October 9, 2019
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
UniQure Biopharma B.V.

Brief Summary:
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 or disease Intervention/treatment Phase
Huntington Disease Genetic: rAAV5-miHTT Procedure: Imitation surgery Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I/II, Randomized, Double-blind, Sham Control Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington Disease
Actual Study Start Date : September 6, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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 Name: 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




Primary Outcome Measures :
  1. Number and type of Adverse Events (AE) [ Time Frame: 18 months ]
    Safety will be assessed by adverse events (AEs) related to clinical safety laboratory tests, vital signs, electrocardiograms (ECGs), neurological and physical examinations, rAAV5 vector shedding, immunogenicity response, suicidality risk [Columbia-Suicide Severity Rating Scale [C-SSRS)], changes in global cognitive functioning [Montreal Cognitive Assessment Scale (MoCA)] and MRI measures of edema, inflammation, volume loss and structural changes.


Secondary Outcome Measures :
  1. Duration of persistence of AMT-130 in the brain [ Time Frame: Collected for duration of study through month 60 ]
    Change over time in levels of AMT-130-derived Vector DNA and miRNA Expression in the Cerebrospinal Fluid (CSF)


Other Outcome Measures:
  1. CSF Mutant Protein (fM) [ Time Frame: Collected for duration of study through month 60 ]
    Will be used as an exploratory biomarker to measure disease progression and responsiveness to AMT-130 treatment.

  2. CSF/Serum Neurofilament Light Chain (pg/mL) [ Time Frame: Collected for duration of study through month 60 ]
    Will be used as an exploratory biomarker to measure disease progression and responsiveness to AMT-130 treatment.

  3. Unified Huntington Disease Rating Scale (UHDRS) [ Time Frame: Collected for duration of study through month 60 ]
    The UHDRS will assess changes from baseline in summary scores of domains of motor function, cognitive function, behavioral function, and functional abilities.

  4. Quantitative Motor (Q-Motor) Testing [ Time Frame: Collected for duration of study through month 60 ]
    Q-Motor testing will measure disease progression and responsiveness to AMT-130 treatment.

  5. Huntington's Disease Cognitive Assessment Battery (HD-CAB) [ Time Frame: Collected for duration of study through month 60 ]
    The HD-CAB measures cognitive dysfunction in late premanifest and early manifest HD patients.

  6. Magnetic Resonance Imaging (MRI) [ Time Frame: Collected for duration of study through month 60 ]
    MRI assessments will include whole brain volume, striatal region volumes, white matter volume, gray matter volume, ventricular volume, cortical thickness, and diffusion MRI measures.

  7. Magnetic Resonance Spectroscopy (MRS) [ Time Frame: Collected for duration of study through month 60 ]
    MRS will be collected using single-voxel point resolved spectroscopy of the left putamen and white matter region immediately adjacent to the left putamen. Neuronal health and gliosis will be evaluated by measuring total N-acetylaspartic acid (neuronal integrity marker) and myoinisitol (reactive astrocytosis marker) levels.

  8. Neuro-QoL Measures [ Time Frame: Collected for duration of study through month 60 ]
    The Neuro-QoL is a brief, reliable, valid, standardized set of patient reported, Health Related Quality of Life (HRQoL) measures for people living with neurological conditions.

  9. HDQLIFE Measures [ Time Frame: Collected for duration of study through month 60 ]
    The HDQLIFE is a measurement system that was designed to provide a brief, reliable and valid assessment of HRQoL in HD and consists of NeuroQoL measures that have been validated in the HD population and several new HD specific measures.

  10. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Collected for duration of study through month 60 ]
    The HADS is a 14-item, self-report measure that has been shown to be reliable and valid for identifying depression and anxiety in adults who are physically ill. Each item is scored from 0 (no anxiety or depression) to 3 (abnormal anxiety or depression) for a maximum total score of 21.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04120493


Contacts
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Contact: Joseph J Higgins, M.D., F.A.A.N. 339-970-7081 amt130_clinical_trials@uniqure.com

Locations
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United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Allison Daley    614-688-8672    Allison.Daley@osumc.edu   
Principal Investigator: Sandra Kostyk, M.D., Ph.D.         
United States, Texas
The University of Texas Recruiting
Houston, Texas, United States, 77030
Contact: Jamie Sims    713-500-7763    Jamie.Sims@uth.tmc.edu   
Principal Investigator: Erin Furr-Stimming, MD         
United States, Virginia
Virginia Commonwealth University VCU School of Medicine, Department of Neurology Recruiting
Richmond, Virginia, United States, 23298
Contact: Kelly C Huckstep, LPN    804-965-4283      
Principal Investigator: Claudia Testa, MD         
Sponsors and Collaborators
UniQure Biopharma B.V.

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Responsible Party: UniQure Biopharma B.V.
ClinicalTrials.gov Identifier: NCT04120493     History of Changes
Other Study ID Numbers: CT-AMT-130-01
First Posted: October 9, 2019    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UniQure Biopharma B.V.:
Gene therapy
AAV (adeno-associated virus)
serotype 5 AAV (adeno-associated virus)
serotype 5
Viral vector
miHTT
muHTT
Huntington Disease (HD)
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Dementia
Chorea
Dyskinesias