Gene Therapy in patients with Mucopolysaccharidosis disease

Phase 1

Conditions: 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
MedDRA version: 21.1Level: PTClassification code 10059318Term: Hepatic cancer stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: PTClassification code 10054889Term: Transaminases increasedSystem Organ Class: 10022891 - Investigations
MedDRA version: 20.0Level: LLTClassification code 10037933Term: Reaction anaphylactic anaphylactoidSystem Organ Class: 100000004870
MedDRA version: 20.0Level: PTClassification code 10019717Term: HepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2016-002328-10-IT

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

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:
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

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 life-threatening).
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 three different doses of drug 2x10^11 gc/kg , 6x10^11 gc/kg , 2x10^12 gc/kg;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>•Urinary GAG excretion levels<br>;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 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 climb test (3MSCT), <br>•Forced vital capacity (FVC) and forced expiratory volume at 1 minute (FEV1) in cooperative subjects.<br>;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<br>•Endurance measured by 6-minute walk test (6MWT) and 3-minute stair climb test (3MSCT) measured at baseline1; 2 days pre-treatment; 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 (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<br><br><br>

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