Gene Therapy in Patients With Mucopolysaccharidosis Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 6 December 2021
• Main ID: NCT03173521
• Date of registration: 12/04/2017
• Prospective Registration: Yes
• Primary sponsor: Fondazione Telethon
• Public title: Gene Therapy in Patients With Mucopolysaccharidosis Disease
• Scientific 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
• Date of first enrolment: July 17, 2017
• Target sample size: 9
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03173521
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Italy, Netherlands, Turkey

Contacts

• Name: Nicola Brunetti-Pierri
• Affiliation: Department of Translational Medicine (DISMET) of "Federico II" University, Naples

Key inclusion & exclusion 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.



Age minimum: 4 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Mucopolysaccharidosis Type VI

Intervention(s)

Biological: AAV2/8.TBG.hARSB

Primary Outcome(s)

Primary efficacy outcome - Urinary GAG levels [Time Frame: 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.]

Safety and tolerability of the IMP administration [Time Frame: 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.]

Secondary Outcome(s)

Secondary efficacy outcome - lung volumes [Time Frame: 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 efficacy outcome - endurance [Time Frame: 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 ID(s)

TIGEM1-MPS VI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors