Gene Therapy in Patients With Mucopolysaccharidosis Disease

Browse trials for

• Mucopolysaccharidoses 145
• Mucopolysaccharidosis VI 32

Keywords

• MPSVI

Mucopolysaccharidoses

145 studies on the registry are indexed under Mucopolysaccharidoses; 11 are open to participants now.

This study's enrollment of 9 is below the median of 15 across 80 interventional studies indexed under Mucopolysaccharidoses.

Lead sponsor

Fondazione Telethon is the lead sponsor of 12 studies on the registry; 3 are open to participants now.

Study arms

• Experimental
  open label

  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.

  Biological: AAV2/8.TBG.hARSB

Interventions

• BiologicalAAV2/8.TBG.hARSB

  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.

Primary outcomes

1. 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).

   Time frame: 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.

2. 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.

   Time frame: 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 outcomes

1. Secondary efficacy outcome - endurance

   Endurance as measured by 6-minute walk test (6MWT) in walking subjects, 3-minute stair climb test (3MSCT) in walking subjects.

   Time frame: From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.

2. Secondary efficacy outcome - lung volumes

   Forced vital capacity (FVC), and forced expiratory volume at 1 second (FEV1) in cooperative subjects.

   Time frame: From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.