Clinical Trial: Safety, Tolerability, Ascending Dose and Dose Frequency Study of rhHNS Via an IDDD in MPS IIIA Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Safety, Tolerability, Ascending Dose and Dose Frequency Study of Recombinant Human Heparan N-Sulfatase (rhHNS) Intrathecal Administration Via an Intrathecal Drug Delivery Device in Patien

Brief Summary:

Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 4 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. The central nervous system (CNS) is the most severely affected organ system in patients with MPS IIIA. In these patients abnormal behaviors include, but are not limited to, aggression and excess motor activity/hyperactivity that contribute to disturbances in sleep.Overall, individuals with MPS IIIA have a marked developmental delay and significantly reduced lifespan of 15 years of age on average.

The purpose of this study is to determine the safety and tolerability of rhHNS via ascending doses administered via an a surgically implanted intrathecal drug delivery device (IDDD) intrathecal (IT) route once monthly for 6 months in patients with MPS IIIA.

Detailed Summary:

Sanfilippo syndrome, or Mucopolysaccharidosis (MPS) III, is a rare lysosomal storage disease (LSD) caused by loss in activity of 1 of 4 enzymes necessary for degradation of the glycosaminoglycan (GAG) heparan sulfate (HS) in lysosomes. MPS IIIA results from deficiency of the enzyme heparan N-sulfatase (sulfamidase). In the absence of this enzyme, intermediates of the HS degradation process accumulate in the lysosomes of neurons and glial cells, with lesser accumulation outside the brain. MPS IIIA symptoms arise on average at 7 months of age, with the average age of diagnosis at 4.5 years for the majority of patients. Patients present a wide spectrum and severity of clinical symptoms. The central nervous system (CNS) is the most severely affected organ system in patients with MPS IIIA, evidenced by deficits in language development, motor skills, and intellectual development. In addition, there are abnormal behaviors including but not limited to aggression and excess motor activity/hyperactivity that contribute to disturbances in sleep.Overall, individuals with MPS IIIA have a marked developmental delay and significantly reduced lifespan of 15 years of age on average.

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

Shire Human Genetic Therapies (Shire HGT) is developing a sulfamidase enzyme replacement therapy (ERT)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 is a multicenter, multiple-dose, dose escalation study designed to evaluate the safety, tolerability, and clinical activity
Sponsor: Shire Human Genetic Therapies, Inc.

Current Primary Outcome: Safety [ Time Frame: Duration of study-~9 months for each patient ]

Original Primary Outcome: Safety [ Time Frame: Duration of study-~9 months for each patient ]

Current Secondary Outcome: To determine (by dose group) the effects of IT administration of rhHNS, as measured by (1) change from baseline values, and (2) comparison to values obtained in a natural history study of untreated patients with MPS IIIA Surrogate Endpoint Trial [ Time Frame: 6 months ]

Original Secondary Outcome: Same as current

Information By: Shire Human Genetic Therapies, Inc.

Dates:
Date Received: June 24, 2010
Date Started: June 2010
Date Completion:
Last Updated: September 28, 2012
Last Verified: September 2012