[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT02716246":3,"trial-entities:NCT02716246":217,"trial-summary:NCT02716246":221},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":23,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":31,"interventions":34,"primary_outcomes":59,"secondary_outcomes":64,"sex":81,"minimum_age":82,"maximum_age":82,"healthy_volunteers":83,"eligibility_criteria":84,"std_ages":126,"locations":130,"central_contacts":189,"overall_officials":197,"references":201,"see_also_links":213},"NCT02716246","ABT-001","Phase I\u002FII\u002FIII Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH","Phase I\u002FII\u002FIII Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA","RECRUITING","2029-03","2026-08","2026-08-21","2016-04-25","Ultragenyx Pharmaceutical Inc","INDUSTRY",true,"The main objective of this study is to evaluate the efficacy and safety of UX111 for the treatment of MPS IIIA.","Open-label, single dose, dose-escalation clinical trial of UX111 (scAAV9.U1a.hSGSH) injected intravenously through a peripheral limb vein. A limited course of prophylactic immunomodulatory (IM) therapy will be administered. At approved sites adjuvant IM therapy may be administered to selected participants. The Principal Investigator and\u002For caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IM therapy. Not all participants may receive adjuvant IM therapy.\n\nThis study was previously posted by Abeona Therapeutics, Inc and was transferred to Ultragenyx in August 2022.",[19,20,21,22],"MPS IIIA","Sanfilippo Syndrome","Sanfilippo A","Mucopolysaccharidosis III",[19,24,25],"Sanfilippo","Gene Therapy","INTERVENTIONAL","TREATMENT",[29,30],"PHASE2","PHASE3",{"count":32,"type":33},36,"ESTIMATED",[35,48,52,55],{"type":36,"name":37,"description":38,"armGroupLabels":39,"otherNames":44},"BIOLOGICAL","UX111","Self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the control of a U1a promoter (scAAV9.U1a.hSGSH) will be delivered one time through a venous catheter inserted into a peripheral limb vein.",[40,41,42,43],"Cohort 1 Low Dose","Cohort 2 Mid Dose","Cohort 3 High Dose","Cohort 4 High Dose (Spain Only)",[45,46,47],"scAAV9.U1a.hSGSH","ABO-102","rebisufligene etisparvovec",{"type":49,"name":50,"armGroupLabels":51},"DRUG","Prophylactic Immunomodulatory (IM) Therapy",[40,41,42],{"type":49,"name":53,"armGroupLabels":54},"Optimized Prophylactic IM Therapy",[43],{"type":49,"name":56,"description":57,"armGroupLabels":58},"Adjuvant IM Therapy","The Principal Investigator and\u002For caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IM therapy. Not all participants may receive adjuvant IM therapy.",[40,41,42,43],[60],{"measure":61,"description":62,"timeFrame":63},"Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) (Disaccharide) Exposure","Exposure is defined as the time-normalized area under the curve (AUC) of the percentage reduction from baseline.","Up to Month 24 Visit",[65,67,70,72,75,77,79],{"measure":66,"timeFrame":63},"Bayley Scales of Infant and Toddler Development-Third Edition (BSITD-III) Cognitive Raw Score Over Time",{"measure":68,"description":69,"timeFrame":63},"CSF Ganglioside Type 2 (GM2) Exposure","Exposure is defined as the time-normalized area under the curve (AUC) of the percentage change from baseline.",{"measure":71,"description":69,"timeFrame":63},"CSF Ganglioside Type 3 (GM3) Exposure",{"measure":73,"timeFrame":74},"Percent Change from Baseline in CSF HS","Baseline, Up to Month 24 Visit",{"measure":76,"timeFrame":63},"BSITD-III Receptive Communication Raw Score Over Time",{"measure":78,"timeFrame":63},"BSITD-III Expressive Communication Raw Score Over Time",{"measure":80,"timeFrame":74},"Percent Change From Baseline in Total Cortical Volume","ALL",null,false,{"inclusion":85,"exclusion":93,"raw_text":125},[86,87,88,89,90,91,92],"Diagnosis of MPS IIIA confirmed by the following methods:","No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and","Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)","Age:","For Cohort 1-3: From birth (participating sites in USA and Australia) OR 6 months (participating sites in Spain) to 2 years of age with no BSITD-III Cognitive Development Quotient (DQ) requirement, or older than 2 years with a BSITD-III Cognitive DQ of 60 or above (participating sites globally).","For Cohort 4 (participating sites in Spain): 3 months to ≤ 2 years of age with no BSITD-III Cognitive DQ requirement or \\> 2 years of age with a BSITD-III Cognitive DQ ≥ 60 (n = up to 6). Up to 2 additional subjects \\> 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ \\\u003C 60 may also be enrolled. •Subjects must be ≥ 6 months of age before UX111 administration. However, subjects may be consented and initiate relevant Screening Procedures and IM treatment \\\u003C 6 months of age. Refer to Section 8.2 for relevant screening procedures •For children ≤ 24 months chronological age who were born prematurely, defined as born at \\\u003C 36 weeks gestational age, the corrected gestational age must be used for determining inclusion •The BSITD-III Cognitive DQ is assessed during the onsite Screening visit, for subjects who require it •The age of the child on the date of the Screening BSITD-III assessment is used to determine the requirement for the BSITD-III Cognitive DQ score.","Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Enrollment as verified by documentation from the subject's primary care physician, and willing to defer vaccines through 6 months after completion of the subject's IM medication, or longer per Principal Investigator (PI) judgment. Emergency use authorization or conditional marketing authorization of coronavirus disease (COVID) vaccines is included unless there is an accepted medical exemption.",[94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124],"Inability to participate in the clinical evaluation as determined by PI","Cohorts 1 to 3 only: Identification of two nonsense or null variants on genetic testing of the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)","At least one S298P mutation in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)","Has evidence of an attenuated phenotype of MPS IIIA, in the judgement of the PI","Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics","Active viral infection based on clinical observations","Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer or precludes the child from participating in the protocol assessments and follow up","Cohorts 1 to 3 only: Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by ELISA binding assay in serum","Cohorts 1-3 only: Subjects with a positive response for the enzyme-linked immunosorbent spot assay (ELISpot) for T-cell responses to AAV9","Cohorts 1-3 only: Serology consistent with exposure to human immunodeficiency virus (HIV), or serology consistent with active hepatitis B or C infection, Cohort 4: Current clinically significant infections (including any requiring systemic treatment including, but not limited to, HIV; hepatitis A, B, or C; varicella zosters virus; human T-cell lymphotropic virus type 1 \\[HTLV-1\\]; tuberculosis; or COVID-19) that would interfere with participation in the study.","Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy","Visual, hearing, or other impairment sufficient to preclude cooperation with neurodevelopmental testing","Uncontrolled seizure disorder","Any item (braces, etc.) or circumstance that would exclude the subject from being able to undergo MRI according to local institutional policy","Any other situation that precludes the subject from undergoing procedures required in this study","Subjects with cardiomyopathy or significant congenital heart abnormalities","The presence of significant non-MPS IlIA related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study","Cohorts 1-3: Abnormal laboratory values Grade 2 or higher as defined in common terminology criteria for adverse events (CTCAE) v4.03 for gamma-glutamyl transferase (GGT), total bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT) and activated partial thromboplastin time (aPTT), Cohort 4: Any of the following abnormal laboratory values from screening assessment:","Aspartate aminotransferase (AST), alanine aminotransferase (ALT), GGT, and\u002For alkaline phosphatase ≥ 2 × upper limit of normal (ULN) and\u002For total bilirubin \\> 1.5 × ULN","Anemia (hemoglobin \\\u003C 10 g\u002FdL)","Leukopenia or leukocytosis (total WBC count \\\u003C 3,000\u002Fmm3 and \\> 15,000\u002Fmm3 respectively)","Abnormal absolute neutrophil count (ANC) of \\\u003C 1000\u002Fmm3","Platelet count \\\u003C 100,000\u002Fmm3","Coagulopathy (international normalized ratio \\[INR\\] \\> 1.5) or aPTT \\> 40 seconds","Renal impairment, defined as estimated glomerular filtration rate (eGFR) below the lower limit of normal (age and sex appropriate) based on Bedside Schwartz equation","Female of childbearing potential who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable)","Cohorts 1-3: Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)","Previous treatment by hematopoietic stem cell transplantation","Previous participation in a gene\u002Fcell therapy or enzyme replacement therapy (ERT) clinical trial","Known hypersensitivity, that in the judgment of the PI, places the subject at increased risk for adverse effects.","Unwilling to avoid consumption of grapefruit juice and the use of strong inhibitors of CYP3A4 and\u002For P-gp (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin), strong inducers of CYP3A4 and\u002For P-gp (eg, rifampin, rifabutin, phenobarbital, carbamazepine, or phenytoin), and St. John's Wort from 30 days prior to Screening through completion of the IM regimen.","Inclusion Criteria:\n\n* Diagnosis of MPS IIIA confirmed by the following methods:\n\n  * No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and\n  * Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)\n* Age:\n\n  * For Cohort 1-3: From birth (participating sites in USA and Australia) OR 6 months (participating sites in Spain) to 2 years of age with no BSITD-III Cognitive Development Quotient (DQ) requirement, or older than 2 years with a BSITD-III Cognitive DQ of 60 or above (participating sites globally).\n  * For Cohort 4 (participating sites in Spain): 3 months to ≤ 2 years of age with no BSITD-III Cognitive DQ requirement or \\> 2 years of age with a BSITD-III Cognitive DQ ≥ 60 (n = up to 6). Up to 2 additional subjects \\> 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ \\\u003C 60 may also be enrolled. •Subjects must be ≥ 6 months of age before UX111 administration. However, subjects may be consented and initiate relevant Screening Procedures and IM treatment \\\u003C 6 months of age. Refer to Section 8.2 for relevant screening procedures •For children ≤ 24 months chronological age who were born prematurely, defined as born at \\\u003C 36 weeks gestational age, the corrected gestational age must be used for determining inclusion •The BSITD-III Cognitive DQ is assessed during the onsite Screening visit, for subjects who require it •The age of the child on the date of the Screening BSITD-III assessment is used to determine the requirement for the BSITD-III Cognitive DQ score.\n* Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Enrollment as verified by documentation from the subject's primary care physician, and willing to defer vaccines through 6 months after completion of the subject's IM medication, or longer per Principal Investigator (PI) judgment. Emergency use authorization or conditional marketing authorization of coronavirus disease (COVID) vaccines is included unless there is an accepted medical exemption.\n\nExclusion Criteria:\n\n* Inability to participate in the clinical evaluation as determined by PI\n* Cohorts 1 to 3 only: Identification of two nonsense or null variants on genetic testing of the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)\n* At least one S298P mutation in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)\n* Has evidence of an attenuated phenotype of MPS IIIA, in the judgement of the PI\n* Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics\n* Active viral infection based on clinical observations\n* Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer or precludes the child from participating in the protocol assessments and follow up\n* Cohorts 1 to 3 only: Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by ELISA binding assay in serum\n* Cohorts 1-3 only: Subjects with a positive response for the enzyme-linked immunosorbent spot assay (ELISpot) for T-cell responses to AAV9\n* Cohorts 1-3 only: Serology consistent with exposure to human immunodeficiency virus (HIV), or serology consistent with active hepatitis B or C infection, Cohort 4: Current clinically significant infections (including any requiring systemic treatment including, but not limited to, HIV; hepatitis A, B, or C; varicella zosters virus; human T-cell lymphotropic virus type 1 \\[HTLV-1\\]; tuberculosis; or COVID-19) that would interfere with participation in the study.\n* Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy\n* Visual, hearing, or other impairment sufficient to preclude cooperation with neurodevelopmental testing\n* Uncontrolled seizure disorder\n* Any item (braces, etc.) or circumstance that would exclude the subject from being able to undergo MRI according to local institutional policy\n* Any other situation that precludes the subject from undergoing procedures required in this study\n* Subjects with cardiomyopathy or significant congenital heart abnormalities\n* The presence of significant non-MPS IlIA related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study\n* Cohorts 1-3: Abnormal laboratory values Grade 2 or higher as defined in common terminology criteria for adverse events (CTCAE) v4.03 for gamma-glutamyl transferase (GGT), total bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT) and activated partial thromboplastin time (aPTT), Cohort 4: Any of the following abnormal laboratory values from screening assessment:\n\n  * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), GGT, and\u002For alkaline phosphatase ≥ 2 × upper limit of normal (ULN) and\u002For total bilirubin \\> 1.5 × ULN\n  * Anemia (hemoglobin \\\u003C 10 g\u002FdL)\n  * Leukopenia or leukocytosis (total WBC count \\\u003C 3,000\u002Fmm3 and \\> 15,000\u002Fmm3 respectively)\n  * Abnormal absolute neutrophil count (ANC) of \\\u003C 1000\u002Fmm3\n  * Platelet count \\\u003C 100,000\u002Fmm3\n  * Coagulopathy (international normalized ratio \\[INR\\] \\> 1.5) or aPTT \\> 40 seconds\n  * Renal impairment, defined as estimated glomerular filtration rate (eGFR) below the lower limit of normal (age and sex appropriate) based on Bedside Schwartz equation\n* Female of childbearing potential who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable)\n* Cohorts 1-3: Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)\n* Previous treatment by hematopoietic stem cell transplantation\n* Previous participation in a gene\u002Fcell therapy or enzyme replacement therapy (ERT) clinical trial\n\nCohort 4 only:\n\n* Known hypersensitivity, that in the judgment of the PI, places the subject at increased risk for adverse effects.\n* Unwilling to avoid consumption of grapefruit juice and the use of strong inhibitors of CYP3A4 and\u002For P-gp (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin), strong inducers of CYP3A4 and\u002For P-gp (eg, rifampin, rifabutin, phenobarbital, carbamazepine, or phenytoin), and St. John's Wort from 30 days prior to Screening through completion of the IM regimen.",[127,128,129],"CHILD","ADULT","OLDER_ADULT",[131,141,149,158,173],{"facility":132,"status":133,"city":134,"state":135,"zip":136,"country":137,"geoPoint":138},"Nationwide Children's Hospital","COMPLETED","Columbus","Ohio","43205","United States",{"lat":139,"lon":140},39.96118,-82.99879,{"facility":142,"status":133,"city":143,"state":144,"zip":145,"country":137,"geoPoint":146},"Children's Hospital of Pittsburgh","Pittsburgh","Pennsylvania","15224",{"lat":147,"lon":148},40.44062,-79.99589,{"facility":150,"status":133,"city":151,"state":152,"zip":153,"country":154,"geoPoint":155},"Women's and Children's Hospital","North Adelaide","South Australia","5006","Australia",{"lat":156,"lon":157},-34.90733,138.59141,{"facility":159,"status":8,"city":160,"state":160,"zip":161,"country":162,"contacts":163,"geoPoint":170},"Vall d'Hebron Barcelona Hospital Campus","Barcelona","08035","Spain",[164,168],{"name":165,"role":166,"email":167},"Mireia del Toro, MD","CONTACT","mireia.deltoro@vallhebron.cat",{"name":165,"role":169},"PRINCIPAL_INVESTIGATOR",{"lat":171,"lon":172},41.38879,2.15899,{"facility":174,"status":8,"city":175,"zip":176,"country":162,"contacts":177,"geoPoint":186},"Hospital Clínico Universitario de Santiago","Santiago de Compostela","15706",[178,181,184],{"name":179,"role":166,"email":180},"Eines Monteagudo, MD","eines.monteagudo.vilavedra@sergas.es",{"name":182,"role":166,"email":183},"Beatriz Martín López-Pardo, MD","beatriz.martin.lopezpardo@sergas.es",{"name":185,"role":169},"Maria Luz Couce, MD",{"lat":187,"lon":188},42.88052,-8.54569,[190,194],{"name":191,"role":166,"phone":192,"email":193},"Patients Contact: Trial Recruitment","1-888-756-8657","trialrecruitment@ultragenyx.com",{"name":195,"role":166,"phone":192,"email":196},"HCPs Contact: Medical Information","medinfo@ultragenyx.com",[198],{"name":199,"affiliation":13,"role":200},"Medical Director","STUDY_DIRECTOR",[202,206,209],{"pmid":203,"type":204,"citation":205},"27331076","BACKGROUND","Fu H, Cataldi MP, Ware TA, Zaraspe K, Meadows AS, Murrey DA, McCarty DM. Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery. Mol Ther Methods Clin Dev. 2016 Jun 8;3:16036. doi: 10.1038\u002Fmtm.2016.36. eCollection 2016.",{"pmid":207,"type":204,"citation":208},"29064732","Fu H, Meadows AS, Pineda RJ, Kunkler KL, Truxal KV, McBride KL, Flanigan KM, McCarty DM. Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy. Hum Gene Ther Clin Dev. 2017 Dec;28(4):187-196. doi: 10.1089\u002Fhumc.2017.109. Epub 2017 Oct 24.",{"pmid":210,"type":211,"citation":212},"32884151","DERIVED","McCurdy VJ, Johnson AK, Gray-Edwards HL, Randle AN, Bradbury AM, Morrison NE, Hwang M, Baker HJ, Cox NR, Sena-Esteves M, Martin DR. Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease. Gene Ther. 2021 Apr;28(3-4):142-154. doi: 10.1038\u002Fs41434-020-00190-1. Epub 2020 Sep 3.",[214],{"label":215,"url":216},"Ultragenyx Transparency Commitment","https:\u002F\u002Fwww.ultragenyx.com\u002Four-research\u002Four-clinical-trial-transparency-commitment\u002F",{"nct_id":4,"conditions":218,"biomarkers":219},[20],[220],"SGSH Gene",{"nct_id":4,"found":15,"summary":222,"prompt_version":232},{"design":223,"status":224,"heading":225,"summary":226,"follow_up":227,"word_count":228,"commitments":229,"compensation":230,"drugs_mentioned":231},"This is an open-label, single-dose, dose-escalation study, meaning everyone knows what treatment is given, and the dose may increase for different groups of participants. It plans to enroll 36 participants.","completed","Gene Therapy for Sanfilippo Syndrome Type A (MPS IIIA)","This study is testing a gene therapy called UX111 (scAAV9.U1a.hSGSH) for Sanfilippo Syndrome Type A (MPS IIIA). UX111 is given once through a vein in your arm. The study also uses different types of immunomodulatory (IM) therapy, which are drugs given to help your body respond to the gene therapy. The main goal is to see how well UX111 works and if it's safe. Researchers will measure levels of a substance called Heparan Sulfate (HS) in your cerebrospinal fluid (the fluid around your brain and spinal cord) for up to 24 months to see if the treatment is successful. To join, you must have a confirmed diagnosis of MPS IIIA through specific enzyme and genetic tests. The study is currently unclear on its recruitment status and plans to enroll 36 participants.","Researchers will measure a key marker in your cerebrospinal fluid for up to 24 months after treatment.",131,"You would receive a one-time intravenous (into a vein) injection of UX111 and a limited course of prophylactic immunomodulatory therapy. Adjuvant immunomodulatory therapy may also be given if your doctor decides it's needed.","Not stated in the trial record.",[37],"v2"]