The clinical trial will be conducted on patients with Mucopolysaccharidosis Type VI. MPS VI is characterized by growth retardation, corneal clouding, cardiac valve disease, organomegaly, skeletal dysplasia, without central nervous system involvement
Conditions
Interventions
Product Name: AAV2/8.TBG.hARSB
Product Code: not applicable
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: AAV2/8.TBG.hARSB
Other descriptive
Sponsors
FONDAZIONE TELETHON
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have a documented biochemical and molecular diagnosis of MPS VI. 2. Subjects must be 4 years old or older. 3. Subjects should have received Enzyme Replacement Therapy (ERT) for at least 12 months before enrolment, and should continue to receive treatment until 7-14 days before IMP administration. 4. Documented informed consent; willingness to adhere to protocol and required long-term follow-up as evidenced by written informed consent. Are the trial subjects under 18? yes Number of subjects for this age range: 8 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Subjects unable or unwilling to meet requirements of the study. 2.History of severe anaphylactoid reaction to Naglazyme in subjects receiving ERT that could affect the safety (severe reaction is meant to be an event with respiratory impairment that is lifethreatening). 3.Serum AST or ALT above the upper limit of normal range at the baseline evaluations (Baseline 2, -5 days). 4. Detectable serum neutralizing antibodies (NAB) against AAV8 vector.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of the drug;Secondary Objective: To investigate the efficacy of the drug;Primary end point(s): • Overall short-term and long-term safety and tolerability measured by recording of adverse events, physical examination including vital signs, laboratory tests and liver ultrasound. • Inflammation of the liver, as shown by an elevation in transaminases. • Kidney fuction by monitoring of parameters: creatinine, albumin, total protein and BUN • Presence of immune-complexes by monitoring of C3 and C4 complement protein level ;Timepoint(s) of evaluation of this end point: The safety endpoints will be monitored in the days immediately following the infusion of the drug (short-term monitoring) and during the following weeks, months and years (monitoring long-term). L 'outcome of efficacy will be evaluated during the three days post treatment and at 4 and 9 months, a year, a year and a half, two years, two and a half years and three years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Leukocyte ARSB levels (enzyme activity), •Endurance measured by 6-minute walk test (6MWT) and 3-minute stair climb test (3MSCT), •Forced vital capacity (FVC) and forced expiratory volume at 1 minute (FEV1) in cooperative subjects.;Timepoint(s) of evaluation of this end point: •Leukocyte ARSB levels (enzyme activity) measured at screening; the day before treatment: 3 weeks post-treatment; 10 weeks post-treatment; 14 weeks post-treatment ; 4,9,12 months post-trattamento1.5, 2, 2.5, 3 years post-treatment •Endurance measured by 6-minute walk test (6MWT) and 3-minute stair climb test (3MSCT) measured at baseline1; 2 days pretreatment; 4,9,12 months post-treatment; 1.5, 2, 2.5, 3 years post-trattamento, •Forced vital capacity (FVC) and forced expiratory volume at 1 minute (FEV1) in cooperative subjects measured at baseline1; 1 o 2 days pre-treatment; 4,9,12 months post-treatment; 1.5, 2, 2.5, 3 years post-treatment | — |
Countries
Italy, Netherlands, Turkey
Contacts
Public ContactSTEFANO ZANCAN
FONDAZIONE TELETHON
Outcome results
None listed