Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB
NCT ID: NCT03315182
Last Updated: 2022-05-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1/PHASE2
11 participants
INTERVENTIONAL
2017-10-16
2022-04-07
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Long-term Follow-up Study of Patients With MPS IIIB Treated With ABO-101
NCT04655911
Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease
NCT04088734
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
NCT02716246
Follow-up Study of AAV-Mediated Gene Transfer (UX111; Previously Known as ABO-102) for MPS Type IIIA
NCT04360265
A Open Label Study in Previously Studied, SBC-103 Treatment Naïve MPS IIIB Subjects to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 Administered Intravenously
NCT02618512
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Cohort 1 (Low Dose) rAAV9.CMV.hNAGLU
Subjects will receive a single infusion:
• Cohort 1 (Low Dose): 2 X 10E13 vg/kg (n=2 participants)
rAAV9.CMV.hNAGLU
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein.
Cohort 2 (Med Dose) rAAV9.CMV.hNAGLU
Subjects will receive a single infusion:
• Cohort 2 (Med Dose): 5 X 10E13 vg/kg (n=4-5 participants)
rAAV9.CMV.hNAGLU
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein.
Cohort 3 (High Dose) rAAV9.CMV.hNAGLU
Subjects will receive a single infusion:
• Cohort 3 (High Dose): 1 X 10E14 vg/kg (n=4-8 participants)
rAAV9.CMV.hNAGLU
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
rAAV9.CMV.hNAGLU
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* No detectable or significantly reduced NAGLU enzyme activity by plasma.
* Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the NAGLU gene
* Age: From Birth to 2 years or children older than 2 years with a minimum cognitive Development Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)
Exclusion Criteria
* Identification of two nonsense or null variants on genetic testing of the NAGLU gene
* Has evidence of an attenuated phenotype of MPS IIIB
* Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
* Active viral infection based on clinical observations as infections by Adenoviruses, Epstein-Barr Virus, Cytomegalovirus, Respiratory Syncytial Virus
* 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 as autoimmune diseases requiring immunosuppression, such as juvenile rheumatoid arthritis or idiopathic thrombocytopenia purpura
* Subjects with total anti-AAV9 antibody titers ≥ 1:100 as determined by ELISA binding immunoassay
* Subjects with a positive response for the ELISPOT for T-cell responses to AAV9
* Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection
* 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 or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing
* Uncontrolled seizure disorder
* Any item (braces, etc.) which 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 IlIB related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
* Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.0 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
* Female participant who is pregnant or demonstrates a positive urine or serum result at screening assessment (if applicable).
* Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
* Previous treatment by Haematopoietic Stem Cell transplantation
* Previous participation in a gene/cell therapy or ERT clinical trial
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Abeona Therapeutics, Inc
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Nationwide Children's Hospital
Columbus, Ohio, United States
Armand-Trousseau Hospital
Paris, , France
University Hospital Hamburg-Eppendorf
Hamburg, , Germany
Hospital Clinico Universitario de Santiago
Santiago de Compostela, , Spain
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Fu H, Dirosario J, Killedar S, Zaraspe K, McCarty DM. Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery. Mol Ther. 2011 Jun;19(6):1025-33. doi: 10.1038/mt.2011.34. Epub 2011 Mar 8.
Truxal KV, Fu H, McCarty DM, McNally KA, Kunkler KL, Zumberge NA, Martin L, Aylward SC, Alfano LN, Berry KM, Lowes LP, Corridore M, McKee C, McBride KL, Flanigan KM. A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: Implications for clinical trial design. Mol Genet Metab. 2016 Nov;119(3):239-248. doi: 10.1016/j.ymgme.2016.08.002. Epub 2016 Aug 18.
Neufeld EF, Cantz MJ. Corrective factors for inborn errors of mucopolysaccharide metabolism. Ann N Y Acad Sci. 1971 Jul 6;179:580-7. doi: 10.1111/j.1749-6632.1971.tb46934.x. No abstract available.
Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ. Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. Eur J Hum Genet. 1999 Jan;7(1):34-44. doi: 10.1038/sj.ejhg.5200242.
Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr. 2013 May;102(5):462-70. doi: 10.1111/apa.12169. Epub 2013 Feb 6.
de Ruijter J, Valstar MJ, Wijburg FA. Mucopolysaccharidosis type III (Sanfilippo Syndrome): emerging treatment strategies. Curr Pharm Biotechnol. 2011 Jun;12(6):923-30. doi: 10.2174/138920111795542651.
Murrey DA, Naughton BJ, Duncan FJ, Meadows AS, Ware TA, Campbell KJ, Bremer WG, Walker CM, Goodchild L, Bolon B, La Perle K, Flanigan KM, McBride KL, McCarty DM, Fu H. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Hum Gene Ther Clin Dev. 2014 Jun;25(2):72-84. doi: 10.1089/humc.2013.208. Epub 2014 Apr 10.
Ribera A, Haurigot V, Garcia M, Marco S, Motas S, Villacampa P, Maggioni L, Leon X, Molas M, Sanchez V, Munoz S, Leborgne C, Moll X, Pumarola M, Mingozzi F, Ruberte J, Anor S, Bosch F. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy. Hum Mol Genet. 2015 Apr 1;24(7):2078-95. doi: 10.1093/hmg/ddu727. Epub 2014 Dec 18.
Hamano K, Hayashi M, Shioda K, Fukatsu R, Mizutani S. Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue. Acta Neuropathol. 2008 May;115(5):547-59. doi: 10.1007/s00401-007-0325-3. Epub 2007 Dec 4.
Tamagawa K, Morimatsu Y, Fujisawa K, Hara A, Taketomi T. Neuropathological study and chemico-pathological correlation in sibling cases of Sanfilippo syndrome type B. Brain Dev. 1985;7(6):599-609. doi: 10.1016/s0387-7604(85)80008-5.
Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr Gene Ther. 2011 Aug;11(4):321-30. doi: 10.2174/156652311796150354.
Saeki I, Tokunaga S, Matsuura T, Hayashida M, Yanagi Y, Taguchi T. A formula for determining the standard liver volume in children: a special reference for neonates and infants. Pediatr Transplant. 2012 May;16(3):244-9. doi: 10.1111/j.1399-3046.2011.01624.x. Epub 2011 Dec 12.
Schlesinger AE, Edgar KA, Boxer LA. Volume of the spleen in children as measured on CT scans: normal standards as a function of body weight. AJR Am J Roentgenol. 1993 May;160(5):1107-9. doi: 10.2214/ajr.160.5.8470587.
Malm G, Mansson JE. Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30-year period. Acta Paediatr. 2010 Aug;99(8):1253-7. doi: 10.1111/j.1651-2227.2010.01800.x. Epub 2010 Mar 14.
Dale DC, Fauci AS, Guerry D IV, Wolff SM. Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone. J Clin Invest. 1975 Oct;56(4):808-13. doi: 10.1172/JCI108159.
Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010 Aug;31(8):318-24. doi: 10.1016/j.it.2010.05.006.
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/s41434-020-00190-1. Epub 2020 Sep 3.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
ABT-002
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.