Gene Therapy in patients with Mucopolysaccharidosis disease

• Register: EUCTR
• Last refreshed on: 12 November 2018
• Main ID: EUCTR2016-002328-10-NL
• Date of registration: 07/11/2018
• Prospective Registration: No
• 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: 29/10/2018
• Target sample size: 10
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002328-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy, Netherlands, Turkey

Contacts

• Name: STEFANO ZANCAN
• Affiliation: FONDAZIONE TELETHON

• Name: STEFANO ZANCAN
• Affiliation: FONDAZIONE TELETHON

Key inclusion & exclusion criteria

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: 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

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 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

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

Intervention(s)

Product Name: AAV2/8.TBG.hARSB
Product Code: not applicable
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: AAV2/8.TBG.hARSB
Other descriptive name: ADENO-ASSOCIATED VIRAL (AAV) SEROTYPE 8 (AAV2/8) VECTOR WITH LIVER-SPECIFIC THYROXINE-BINDING GLOBULIN (TBG) PROMOTER, DRIVING THE EXPRESSION OF THE HUMAN ARSB GENE
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 25900000000000-

Primary Outcome(s)

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.
• Inflammation of the liver, as shown by an elevation in transaminases.
• Kidney fuction by monitoring of parameters: creatinine, albumin, total protein and BUN
• Presence of immune-complexes by monitoring of C3 and C4 complement protein level

Main Objective: To evaluate the safety of the drug

Secondary Objective: To investigate the efficacy of the drug

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(s)

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
•Endurance measured by 6-minute walk test (6MWT) and 3-minute stair
climb test (3MSCT) measured at baseline1; 2 days pretreatment;
4,9,12 months post-treatment; 1.5, 2, 2.5, 3 years post-trattamento,
•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

Secondary end point(s): •Leukocyte ARSB levels (enzyme activity),
•Endurance measured by 6-minute walk test (6MWT) and 3-minute stair
climb test (3MSCT),
•Forced vital capacity (FVC) and forced expiratory volume at 1 minute
(FEV1) in cooperative subjects.

Secondary ID(s)

TIGEM1-MPSVI

Source(s) of Monetary Support

FONDAZIONE TELETHON