Conditions: Sanfilippo Syndrome
Keywords: sulfoglucosamine sulfohydrolase (SGSH) recombinant human heparan N-sulfatase (rhHNS) Hunter's Syndrome Shire HGT Lysosomal Storage Disease (LSD) Sanfilippo Syndrome Type A (Sanfilippo A) enzyme replacement therapy (ERT)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 21
Healthy volunteers: no

Brief summary:
Sanfilippo syndrome Type A, or Mucopolysaccharidosis (MPS) IIIA, is a rare lysosomal storage disease caused by deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, there is an accumulation of the glycosaminoglycan, heparan sulfate, resulting in progressive neurodegeneration. Symptoms are usually first noted in the 1st or 2nd year of life, although definitive diagnosis is often delayed, with an average age of diagnosis of 4.5 years. The disease is characterized by developmental delays initially, followed by neurological developmental arrest, then regression. These developmental deficits are typically associated with severe behavioral disturbances. Patients have a significantly reduced lifespan, with few surviving beyond the 2nd or 3rd decade.

The purpose of this study is to evaluate the safety and efficacy of recombinant human heparan-N-sulfatase (rhHNS) in pediatric patients with Early Stage Mucopolysaccharidosis Type III A Disease.

Detailed description:
No effective, disease-modifying therapies are currently approved as treatments for this devastating and disabling disease.

Shire Human Genetic Therapies (Shire HGT) is developing an enzyme replacement therapy (ERT) recombinant human heparan-N-sulfatase (rhHNS) for patients with MPS IIIA. rhHNS is being administered into the cerebrospinal fluid (CSF) via an surgically implanted intrathecal drug delivery device (IDDD), because when administered intravenously (IV) it does not cross the blood brain barrier (BBB).

This study will evaluate the effect of 48 weeks of rhHNS treatment on the clinical course of MPS IIIA, using cognitive function as the primary outcome measure. The trial will evaluate 2 dosing regimens of rhHNS administered via an IDDD in comparison with a no treatment control group. Patients will be randomized 1:1:1 to either of the treatment groups or the no treatment group. Treatment will be administered in an open-label manner. The safety and tolerability profile of rhHNS will continue to be evaluated in this study.

Arms:
arm 1: rhHNS 45 mg administered intrathecally Q2W (once every 2 weeks ie, every 14 days), for 48 weeks via the surgically implanted IDDD (or LP) arm 2: rhHNS 45 mg administered intrathecally Q4W (once every 4 weeks ie, every 28 days), for 48 weeks via the surgically implanted IDDD (or LP) arm 3: The comparator group will receive no treatment with rhHNS.

Interventions: intervention 1: Recombinant human heparan N-sulfatase [rhHNS]
Intervention descriptions: intervention 1: Recombinant human heparan N-sulfatase \[rhHNS\]

Protocol document: