Clinical trial NCT03173521: Gene Therapy in Patients With Mucopolysaccharidosis Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Mucopolysaccharidosis Type VI
Keywords: MPSVI
Lead sponsor: Fondazione Telethon
Sponsor class: OTHER
First posted: 2017-06-02
Enrollment: 9
Sex: ALL
Minimum age (years): 4
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Mucopolysaccharidosis type VI disease is involved in Lysosomal Storage Disorder. The MPS VI disease is characterized by growth retardation, corneal clouding, cardiac valve disease, organomegaly, skeletal dysplasia, without central nervous system involvement.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of the IMP administration
timeFrame: 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.
measure: Primary efficacy outcome - Urinary GAG levels
timeFrame: 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:
measure: Secondary efficacy outcome - endurance
timeFrame: From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.
measure: Secondary efficacy outcome - lung volumes
timeFrame: From GT up to 5 years post IMP administration at the following visits: months 4,9,12; years 1.5, 2, 2.5, 3.
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Department of Translational Medicine (DISMET) of "Federico II" University, Naples
city: Ankara
country: Turkey
facility: Children's Hospital Hacettepe University
Study officials:
affiliation: Department of Translational Medicine (DISMET) of "Federico II" University, Naples
name: Nicola Brunetti-Pierri
role: PRINCIPAL_INVESTIGATOR
References: