A Phase I/II Open Label, Dose Escalation, Safety Study in Subjects With Mucopolysaccharidosis Type VI (MPS VI) Using Adeno-Associated Viral Vector 8 to Deliver the Human ARSB Gene to Liver
Sponsor study identifier
interventional
9
2 countries
2
Study Start
July 17, 2017
Actual (reported)Primary Completion
July 30, 2021
Actual (reported)Study Completion
July 16, 2024
Actual (reported)This study investigated the safety and efficacy of gene therapy approaches for Mucopolysaccharidosis type VI disease caused by the deficiency of arylsulfatase B (ARSB) enzyme. The aim of the study is to evaluate the safety and efficacy of the treatment.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
July 16, 2024
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
April 12, 2017
Actual (reported)June 2, 2017
Actual (reported)July 17, 2017
Actual (reported)July 30, 2021
Actual (reported)July 16, 2024
Actual (reported)Safety and tolerability of the IMP administration
Overall safety and tolerability will be determined through monitoring of adverse events, laboratory and clinical investigations and imaging studies (for example complete physical examination with vital signs recording, liver ultrasound, measurement of transaminases, thyroids hormones, creatinine, albumin, total proteins in blood and urine, and urea, C3 and C4 in blood).
From GT up to 5 years post IMP administration at the following visits: days 1,2,3; weeks 2,3,6,7,8,9,10,11,12,13,14; months 4,9,12; years 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5.
Primary efficacy outcome - Urinary GAG levels
To determine the efficacy of gene therapy, post-injection urinary GAG excretion levels will be compared to the average of pre-injection urinary GAG determined at baseline 1 and at visit 1.
From GT up to 5 years post IMP administration at the following visits: days 1,2,3; months 4,9,12,15; years 1.5,1.75, 2, 2.5, 3, 4, 5.
Secondary efficacy outcome - endurance
From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.
Secondary efficacy outcome - lung volumes
From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.
Adeno-associated viral vector serotype 8 with liver-specific thyroxine-binding globulin (TBG) promoter driving the expression of the human ARSB gene diluted in its final formulation medium \[Drug product (DP) diluted in 0.9% saline solution and 0.25% of human serum albumin\]. Four dose levels are available: * 'Starting dose' is 6x1011 gc of vector per kg of body weight. * 'High dose' is 2x1012 gc of vector per kg of body weight. * 'Very high dose' is 6x1012 gc of vector per kg of body weight. * 'Low dose' is 2x1011 gc of vector per kg of body weight. Intermediate doses are also possible. The administration of the IMP will be performed into a peripheral vein (e.g. median cubital vein) over 2-4 hours using an infusion pump. The IMP final volume to be injected is calculated based on the patient's weight (determined on the day of hospital admission), as 3 mL/kg.
Adeno-associated viral vector serotype 8 with liver-specific thyroxinebinding globulin (TBG) promoter driving the expression of the human ARSB gene. Four dose levels are available: * Starting dose is 6x1011 gc of vector per kg of body weight; * High dose is 2x1012 gc of vector per kg of body weight and will be administered after at least two subjects at the starting dose have experienced no DLT; * Very high dose is 6x1012 vector per kg of body weight and will be administered after three subjects at the high dose have experienced no DLT; * Low dose is 2x1011 gc of vector per kg of body weight. Intermediate doses are also possible. The administration of the IMP will be performed into a peripheral vein. The IMP final volume to be injected is calculated based on the patient's weight (determined on the day of hospital admission), as 3 mL/kg.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Department of Translational Medicine (DISMET) of "Federico II" University, Naples
Naples, 80131, Italy
Children's Hospital Hacettepe University
Ankara, Turkey (Türkiye)
Rossi A, Romano R, Fecarotta S, Dell'Anno M, Pecorella V, Passeggio R, Zancan S, Parenti G, Santamaria F, Borgia F, Deodato F, Funghini S, Rupar CA, Prasad C, O'Callaghan M, Mitchell JJ, Valsecchi MG, la Marca G, Galimberti S, Auricchio A, Brunetti-Pierri N. Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy. Med. 2025 Apr 11;6(4):100544. doi: 10.1016/j.medj.2024.10.021. Epub 2024 Nov 14.
Brunetti-Pierri N, Ferla R, Ginocchio VM, Rossi A, Fecarotta S, Romano R, Parenti G, Yildiz Y, Zancan S, Pecorella V, Dell'Anno M, Graziano M, Alliegro M, Andria G, Santamaria F, Brunetti-Pierri R, Simonelli F, Nigro V, Vargas M, Servillo G, Borgia F, Soscia E, Gargaro M, Funghini S, Tedesco N, Le Brun PR, Rupar CA, Prasad C, O'Callaghan M, Mitchell JJ, Danos O, Marteau JB, Galimberti S, Valsecchi MG, Veron P, Mingozzi F, Fallarino F, la Marca G, Sivri HS, Auricchio A. Liver-Directed Adeno-Associated Virus-Mediated Gene Therapy for Mucopolysaccharidosis Type VI. NEJM Evid. 2022 Jul;1(7):EVIDoa2200052. doi: 10.1056/EVIDoa2200052. Epub 2022 Jun 6.
Nicola Brunetti-Pierri
Department of Translational Medicine (DISMET) of "Federico II" University, Naples
9 participants (actual enrollment reported by the registry).
First Submitted
April 12, 2017
First Posted
June 2, 2017
Study Start
July 17, 2017
Actual (reported)Study of Recombinant Human N-acetylgalactosamine 4-sulfatase (rhASB) in Patients With MPS VI
Contact the study team to confirm eligibility.
Primary Completion
July 30, 2021
Actual (reported)Study Completion
July 16, 2024
Actual (reported)Last Updated
November 22, 2024
Record last verified: 2024-11
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