Mucopolysaccharidosis Type VI Clinical Trial
Official title:
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
Verified date | November 2021 |
Source | Fondazione Telethon |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 9 |
Est. completion date | September 30, 2025 |
Est. primary completion date | June 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 4 Years to 65 Years |
Eligibility | Inclusion Criteria: 1. Documented biochemical and molecular diagnosis of MPS VI. Testing for homozygous or compound heterozygous disease-causing mutations of the ARSB gene must have been performed by an accredited laboratory. 2. Subjects must be of 4 years of age or older. 3. Subjects should have received ERT for at least 12 months before enrolment and should continue to receive ERT until 7-14 days before IMP administration. 4. Documented informed consent; willingness to adhere to protocol and to participate to long-term follow-up, as evidenced by written informed consent. Exclusion Criteria: 1. Subjects unable or unwilling to meet requirements of the study. 2. Participation in a clinical study with an investigational drug in the 6 months prior to enrolment in this trial. 3. Subjects unable to perform the 6MWT. 4. History of severe anaphylactoid reaction to Naglazyme in subjects receiving ERT that could affect the safety (severe reaction is meant to be a respiratory impairment event that is life-threatening). 5. Presence of tracheostomy or need of ventilatory assistance. 6. Subjects with evidence of progressive myelomalacia that is considered severe enough to require neck surgery in the first six months after enrolment. 7. Values of AST or ALT above the upper limit of normal range at baseline 2 (at -5days) evaluations. 8. Co-existence of chronic diseases or clinically relevant abnormal baseline laboratory values; infections with hepatitis B, C, or HIV (Baseline 1). 9. Systemic corticosteroid therapy or other immunosuppressive/immunomodulating drugs within 2 months prior to IMP administration. 10. Female individuals of childbearing age who are pregnant or nursing or unwilling to use effective contraception for at least one year post-IMP administration. 11. Fertile male individuals who are unwilling to use male barrier contraceptives such as condom. 12. Any other condition that would not allow the subject to complete follow-up examinations during the course of the study and that, in the opinion of the Investigator, would make the subject unsuitable for the study. 13. Presence of serum NAB to AAV8 above the limit of detection of the assay (Screening and Baseline 1). 14. Presence of serum antibodies anti-ARSB above the upper limit of detection of the assay (antibodies anti-ARSB level >31250 or declared positive at the value of serum dilution 1.10 according to the performed assay) at Screening and Baseline 1. |
Country | Name | City | State |
---|---|---|---|
Italy | Department of Translational Medicine (DISMET) of "Federico II" University, Naples | Naples | |
Turkey | Children's Hospital Hacettepe University | Ankara |
Lead Sponsor | Collaborator |
---|---|
Fondazione Telethon |
Italy, Turkey,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 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 | 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. | 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 | Secondary efficacy outcome - lung volumes | Forced vital capacity (FVC), and forced expiratory volume at 1 second (FEV1) in cooperative subjects. | From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3. |
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