Ignite Creation Date:
2025-12-25 @ 1:10 AM
Ignite Modification Date:
2026-02-25 @ 5:51 PM
Study NCT ID:
NCT04120493
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-21
First Post:
2019-09-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006816', 'term': 'Huntington Disease'}], 'ancestors': [{'id': 'D001480', 'term': 'Basal Ganglia Diseases'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003704', 'term': 'Dementia'}, {'id': 'D002819', 'term': 'Chorea'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009069', 'term': 'Movement Disorders'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D003072', 'term': 'Cognition Disorders'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C005703', 'term': 'salicylhydroxamic acid'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 43}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2019-09-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2029-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-17', 'studyFirstSubmitDate': '2019-09-30', 'studyFirstSubmitQcDate': '2019-10-07', 'lastUpdatePostDateStruct': {'date': '2025-10-21', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2019-10-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'CSF Mutant Protein (fM)', 'timeFrame': 'Collected for duration of study through month 72', 'description': 'Will be used as an exploratory biomarker to measure disease progression and responsiveness to AMT-130 treatment.'}, {'measure': 'CSF/Serum Neurofilament Light Chain (pg/mL)', 'timeFrame': 'Collected for duration of study through month 72', 'description': 'Will be used as an exploratory biomarker to measure disease progression and responsiveness to AMT-130 treatment.'}, {'measure': 'Unified Huntington Disease Rating Scale (UHDRS)', 'timeFrame': 'Collected for duration of study through month 72', 'description': 'The UHDRS will assess changes from baseline in summary scores of domains of motor function, cognitive function, behavioral function, and functional abilities.'}, {'measure': 'Quantitative Motor (Q-Motor) Testing', 'timeFrame': 'Collected for duration of study through month 72 (Cohorts 1, 2 & 3)', 'description': 'Q-Motor testing will measure disease progression and responsiveness to AMT-130 treatment.'}, {'measure': 'Magnetic Resonance Imaging (MRI)', 'timeFrame': 'Collected for duration of study through month 72', 'description': 'MRI assessments will include whole brain volume, striatal region volumes, white matter volume, gray matter volume, ventricular volume, cortical thickness, and diffusion MRI measures.'}, {'measure': 'Neuro-QoL Measures', 'timeFrame': 'Collected for duration of study through month 72', 'description': '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.'}], 'primaryOutcomes': [{'measure': 'Number and type of Adverse Events (AE)', 'timeFrame': '12 months (Cohorts 1 & 2) and 12 months (Cohort 3)', 'description': '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 (Cohorts 1, 2 \\& 3), 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.'}], 'secondaryOutcomes': [{'measure': 'Duration of persistence of AMT-130 in the brain', 'timeFrame': 'Collected for duration of study through month 72 (Cohorts 1 & 2) and through month 16 (Cohorts 3 & 4)', 'description': 'Change over time in levels of AMT-130-derived Vector DNA Expression in the Cerebrospinal Fluid (CSF)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Gene therapy', 'AAV (adeno-associated virus)', 'serotype 5 AAV (adeno-associated virus)', 'serotype 5', 'Viral vector', 'miHTT', 'muHTT', "Huntington's Disease (HD)"], 'conditions': ["Huntington's Disease"]}, 'referencesModule': {'references': [{'pmid': '40235521', 'type': 'DERIVED', 'citation': "Pala M, Yilmaz SG. Circular RNAs, miRNAs, and Exosomes: Their Roles and Importance in Amyloid-Beta and Tau Pathologies in Alzheimer's Disease. Neural Plast. 2025 Apr 8;2025:9581369. doi: 10.1155/np/9581369. eCollection 2025."}, {'pmid': '38489195', 'type': 'DERIVED', 'citation': "Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: March 2024. J Huntingtons Dis. 2024;13(1):1-14. doi: 10.3233/JHD-240017."}, {'pmid': '36463457', 'type': 'DERIVED', 'citation': "Estevez-Fraga C, Tabrizi SJ, Wild EJ. Huntington's Disease Clinical Trials Corner: November 2022. J Huntingtons Dis. 2022;11(4):351-367. doi: 10.3233/JHD-229006."}, {'pmid': '32250312', 'type': 'DERIVED', 'citation': "Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: April 2020. J Huntingtons Dis. 2020;9(2):185-197. doi: 10.3233/JHD-200002."}]}, 'descriptionModule': {'briefSummary': '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 1/2, multicenter, first-in-human (FIH) study. The first three cohorts of the study have completed enrollment, including the randomized, double-blind, sham-controlled cohorts. Cohort 4 is open-label.\n\nCohort 4 participants will receive high dose AMT-130.', 'detailedDescription': "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's Disease signs in animal models.\n\nCohort 1, 2, and 3 evaluated low dose and high dose AMT-130.\n\nCohort 4 will further evaluate the safety of high dose AMT-130 in participants with low striatal volume. All participants in Cohort 4 will receive high dose AMT-130 and will receive pre- and post-operative dexamethasone.\n\nCohorts 1 and 2 participants continue follow-up visits through 6 years after receipt of AMT-130. Cohorts 3 and 4 participants continue follow-up visits through 5 years after receipt of AMT-130."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '25 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Able and willing to provide written informed consent prior to the study and study-related procedure\n* Participants 25 to 65 years of age of both sexes\n* Cohorts 1, 2, \\& 4: Early manifest HD as defined by a UHDRS total functional capacity (TFC) score of 9 to 13 and EITHER a diagnostic confidence 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\n* Cohort 3: Early manifest HD as defined by a UHDRS TFC score of ≥ 11 and EITHER a DCL of 4 or a DCL of 3 with either a positive "Yes" response to UHDRS Question 80 (multidimensional manifest diagnosis on motor, cognitive, behavioral, functional) or DSM5 criteria for cognitive disorder (Movement Disorder Society Task Force criteria).\n* HTT gene expansion testing with the presence of ≥40 CAG repeats\n* Striatal MRI volume requirements per hemisphere:\n* Cohorts 1, 2, \\& 3: Putamen ≥2.5 cm\\^3 (per side); Caudate ≥2.0 cm\\^3 (per side)\n* Cohort 4: Putamen \\<2.5 cm\\^3 (on either side); Caudate \\<2.0 cm\\^3 (on either side)\n* All HD concomitant medications (addressing motor, behavioral, and cognitive symptoms) must be stable for 3 months prior to Screening with no change in clinical symptoms requiring change in medication prior to anticipated administration procedure\n* Able and willing to comply with all procedures and the study visit schedule as outlined in the protocol\n* All female participants of childbearing potential (FOCP) must have a negative serum pregnancy test at Screening, (and Visit 1A, as appropriate), a negative pregnancy urine dipstick at Baseline, and not be breastfeeding. All FOCPs and sexually mature males must be compliant with a highly effective birth control method.\n\nExclusion Criteria:\n\n* Evidence of suicide risk\n* Receipt of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.\n* Participation in an investigational trial or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation) within 60 days prior to Screening or anytime over the duration of this study.\n* Presence of an implanted deep brain stimulation device, ventriculoperitoneal or other CSF shunt, or other implanted catheter\n* Any history of gene therapy, RNA or DNA targeted HD specific investigational agents, such as antisense oligonucleotides (ASOs), cell transplantation or any other experimental brain surgery.\n* Any contraindication to 3.0 Tesla MRI as per local guidelines\n* Brain and spinal pathology that may interfere with the surgical delivery of AMT-130 or represents a significant neurologic comorbid disorder\n* Any contraindication to lumbar puncture as per local guidelines\n* Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated\n* Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study\n* Current or recurrent disease, (including pre-existing cardiovascular or pulmonary conditions) infection, or other significant concurrent medical condition or medications that could confound clinical and laboratory evaluations or could affect a participant\'s safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule\n* Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients\n* Any known allergy to gadoteridol (ProHance)\n* Screening laboratory values (as measured by the central laboratory): a. Alanine aminotransferase (ALT) \\>2 × upper limit of normal (ULN) b. Aspartate aminotransferase (AST) \\>2 × ULN c. Total bilirubin \\>2 × ULN d. Alkaline phosphatase (ALP) \\>2 × ULN e. Creatinine \\>1.5 × ULN f. Platelet count \\<100,000/mm3g.Prothrombin time (PT) \\>1.2 × ULN h. Partial thromboplastin time (PTT) \\>1.2 × ULN\n* Known allergy, sensitivity, or other contraindication to medications in the immunosuppression regimen in this protocol.\n* Any participant with an active infection (e.g., coronavirus disease 2019 \\[COVID-19\\]) at Screening or at the time of treatment that requires medical intervention. Participants may rescreen, or if screened eligible and an open surgical slot is available, may receive treatment after recovery.\n* Cohort 4 ONLY: Inability to establish a safe trajectory to administer AMT-130 to the target structures, as assessed by neuroimaging.'}, 'identificationModule': {'nctId': 'NCT04120493', 'briefTitle': "Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease", 'organization': {'class': 'INDUSTRY', 'fullName': 'UniQure Biopharma B.V.'}, 'officialTitle': "A Phase 1/2, Randomized, Double-Blind, Sham Control and Open-Label Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington's Disease", 'orgStudyIdInfo': {'id': 'CT-AMT-130-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1', 'description': 'Low dose rAAV5-miHTT (6x10\\^12 gc/subject).\n\nNote: gc = genome copies', 'interventionNames': ['Genetic: intra-striatal rAAV5-miHTT']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2', 'description': 'High dose rAAV5-miHTT (6x10\\^13 gc/subject).', 'interventionNames': ['Genetic: intra-striatal rAAV5-miHTT']}, {'type': 'SHAM_COMPARATOR', 'label': 'Cohorts 1, 2', 'description': 'Imitation (sham) surgery', 'interventionNames': ['Other: Imitation (sham) surgery']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 3', 'description': 'Low dose rAAV5-miHTT (6x10\\^12 gc/subject).\n\nHigh dose rAAV5-miHTT (6x10\\^13 gc/subject).', 'interventionNames': ['Genetic: intra-striatal rAAV5-miHTT']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 4', 'description': 'High dose rAAV5-miHTT (6x10\\^13 gc/subject).', 'interventionNames': ['Genetic: intra-striatal rAAV5-miHTT']}], 'interventions': [{'name': 'intra-striatal rAAV5-miHTT', 'type': 'GENETIC', 'otherNames': ['AMT-130'], 'description': 'One time MRI-guided stereotaxic infusion of rAAV5-miHTT into the brain', 'armGroupLabels': ['Cohort 1', 'Cohort 2', 'Cohort 3', 'Cohort 4']}, {'name': 'Imitation (sham) surgery', 'type': 'OTHER', 'description': 'Simulated surgical procedure with skin incisions only; no intrastriatal injections and no burr holes through the skull', 'armGroupLabels': ['Cohorts 1, 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35294-0111', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama at Birmingham', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '85724', 'city': 'Tucson', 'state': 'Arizona', 'country': 'United States', 'facility': 'University of Arizona (Surgical Site Only)', 'geoPoint': {'lat': 32.22174, 'lon': -110.92648}}, {'zip': '94158', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80113', 'city': 'Englewood', 'state': 'Colorado', 'country': 'United States', 'facility': 'CenExel Rocky Mountain Clinical Research', 'geoPoint': {'lat': 39.64777, 'lon': -104.98776}}, {'zip': '60612', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Rush University Medical Center', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '21287', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins University', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '48105', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'University of Michigan Department of Neurology', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '43210', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': 'Ohio State University', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt University Medical Center', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '23298', 'city': 'Richmond', 'state': 'Virginia', 'country': 'United States', 'facility': 'Virginia Commonwealth University VCU School of Medicine, Department of Neurology', 'geoPoint': {'lat': 37.55376, 'lon': -77.46026}}, {'zip': '98195', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'University of Washington Medical Center', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'David H. Margolin, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'uniQure, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'UniQure Biopharma B.V.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}