A Study to Assess the Safety and Tolerability of SOBI003 in Pediatric MPS IIIA Patients

An Open, Non-controlled, Parallel, Ascending Multiple-dose, Multicenter Study to Assess Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of SOBI003 in Pediatric MPS IIIA Patients

MPS IIIA, also known as Sanfilippo A, is an inherited lysosomal storage disease (LSD). MPS IIIA is caused by a deficiency in sulfamidase, one of the enzymes involved in the lysosomal degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The natural course of MPS IIIA is characterized by devastating neurodegeneration with initially mild somatic involvement. The aims of the present study is to assess the dose related safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SOBI003, a chemically modified recombinant human (rh) Sulfamidase developed as an enzyme replacement therapy (ERT).

This is an open-label, non-controlled, parallel, sequential ascending multiple-dose, multicenter study to assess the dose related safety, tolerability, PK and PD of SOBI003 in pediatric MPS IIIA patients. Patients between 1 and 6 years of age who have not received previous treatment for MPS IIIA with an ERT, gene- or stem cell therapy will be eligible to participate in the study. The study is planned to consist of 3 dose cohorts, each comprising 3 patients. Treatment initiations will be staggered within each cohort in order to be able to observe, interpret and treat possible adverse reactions. SOBI003 is administered as weekly i.v. infusions over a period of 24 weeks. Upon completion of the 24-week treatment period with satisfactory tolerability, the patient is offered to receive continued SOBI003 treatment by participation in an extension study.

Inclusion Criteria:

1. Informed consent obtained from the patient's legally authorized representative(s)

2. Patients with MPS IIIA, as confirmed by both:

   • A documented deficiency in sulfamidase enzyme activity in concordance with a diagnosis of MPS IIIA, and
   • Normal enzyme activity level of at least one other sulfatase measured in leukocytes

3. Chronological age of ≥12 and ≤72 months (i.e., 1 to 6 years) at the time of the first SOBI003 infusion and a developmental age ≥12 months at screening as assessed by the Vineland Adaptive Behavior Scales, Second Edition (VABS-II)

4. Medically stable patient who is expected to be able to comply with study procedures

Exclusion Criteria:

1. At least one S298P mutation in the SGSH gene
2. Contraindications for anesthetic procedures, surgical procedure (venous access port) MRI scans and/or lumbar punctures
3. History of poorly controlled seizures
4. Patients is currently receiving psychotropic or other medications which in the investigator's opinion, would be likely to substantially confound test results
5. Significant non-MPS IIIA-related central nervous system (CNS) impairment or behavioral disturbances, which in the investigator's opinion, would confound the scientific integrity or interpretation of study assessments
6. Prior administration of stem cell or gene therapy, or ERT for MPS IIIA
7. Concurrent or prior (within 30 days of enrolment into this study) participation in a study involving invasive procedures