Gene Therapy in patients with Mucopolysaccharidosis disease
- Conditions
- The clinical trial will be conducted on patients withMucopolysaccharidosis Type VI. MPS VI is characterized by growthretardation, corneal clouding, cardiac valve disease, organomegaly, skeletal dysplasia, without central nervous system involvementTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2016-002328-10-NL
- Lead Sponsor
- FONDAZIONE TELETHO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 10
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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. <br>•Inflammation of the liver, as shown by an elevation in transaminases. <br>•Kidney fuction by monitoring of parameters: creatinine, albumin, total protein and BUN <br>•Presence of immune-complexes by monitoring of C3 and C4 complement protein level <br>;Timepoint(s) of evaluation of this end point: The safety endpoints will be monitored in the days immediately following<br>the infusion of the drug (short-term<br>monitoring) and during the following weeks, months and years<br>(monitoring long-term). L 'outcome of efficacy will be evaluated<br>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<br>years.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Leukocyte ARSB levels (enzyme activity),<br>•Endurance measured by 6-minute walk test (6MWT) and 3-minute stair<br>climb test (3MSCT),<br>•Forced vital capacity (FVC) and forced expiratory volume at 1 minute<br>(FEV1) in cooperative subjects.;Timepoint(s) of evaluation of this end point: •Leukocyte ARSB levels (enzyme activity) measured at screening; the<br>day before treatment: 3 weeks post-treatment;<br>10 weeks post-treatment; 14 weeks post-treatment ; 4,9,12 months<br>post-trattamento1.5, 2, 2.5, 3 years post-treatment<br>•Endurance measured by 6-minute walk test (6MWT) and 3-minute stair<br>climb test (3MSCT) measured at baseline1; 2 days pretreatment;<br>4,9,12 months post-treatment; 1.5, 2, 2.5, 3 years post-trattamento,<br>•Forced vital capacity (FVC) and forced expiratory volume at 1 minute<br>(FEV1) in cooperative subjects measured at baseline1; 1 o<br>2 days pre-treatment; 4,9,12 months post-treatment; 1.5, 2, 2.5, 3 years<br>post-treatment