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 : June 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Huntington Disease||Genetic: rAAV5-miHTT Procedure: Imitation surgery||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
Experimental: Cohort 1
Intrastriatal administration of low dose rAAV5-miHTT (6E12 gc/subject). Single dose administration.
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.
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
- 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.
- 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)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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
|Contact: David Cooper, MD, MBAfirstname.lastname@example.org|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94158|
|Contact: Julia Glueck 415-502-7640 email@example.com|
|Principal Investigator: Michael Geschwind, MD, Ph.D.|
|United States, Michigan|
|University of Michigan Department of Neurology||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48105|
|Contact: Angela Stovall 734-647-4787 firstname.lastname@example.org|
|Principal Investigator: Praveen Dayalu, MD|
|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|
|United States, Washington|
|University of Washington Medical Center||Recruiting|
|Seattle, Washington, United States, 98195|
|Contact: Debra Del Castillo 206-543-3647 email@example.com|
|Principal Investigator: Ali Samii, MD|