Phase 1/2 study of BMN 110 in subjects with MPS IVA

• Research type

  Research Study

• Full title

  A Phase 1/2, Multicenter, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects with Mucopolysaccharidosis IVA (Morquio Syndrome)

• IRAS ID

  8176

• Sponsor organisation

  BioMarin Pharmaceutical Inc.

• Eudract number

  2008-007365-23

• ISRCTN Number

  N/A

• Research summary

  Mucopolysaccharidosis IV type A (MPS IVA, also known as Morquio Syndrome) is a rare chemical disease characterized by deficient activity of an enzyme called N acetylgalactosamine 6 sulfatase (GALNS) causing excessive lysosomal storage of a chemical called keratan sulfate (KS). This excessive lysosomal storage causes chemicals to accumulate in many body systems causing abnormalities of bones, joints and short stature, all of which limit mobility and endurance. Malformation of the chest wall and ribs cause impairment of respiratory function with normally death in early adulthood. Abnormality of the neck spine cause instability of the cervical spine that my lead to pressure on the cord with loss of function. Other symptoms may include hearing loss, raised intr-ocular pressure which may impair vision, and leaky heart valves that may predispose them to early heart failure or valve disease. Currently, no satisfactory treatment for MPS IVA exists. Enzyme replacement therapy (ERT) is a potential new treatment option for MPS IVA. ERT is expected to reduce KS storage in affected tissues, including macrophages and cartilage, potentially leading to improvement in respiratory function and endurance. This study will examine weekly, 4 hour infusions of the recombinant version of N acetylgalactosamine 6 sulfatase (BMN 110) in a small group of subjects with MPS IVA. Subjects (20 approximately) will be recruited from the ongoing cross-sectional study in patients with MPS IVA. The safety of increasing doses of BMN 110 every 12 weeks for 3 dose levels will be investigated, and the optimal dose for reducing the elevated KS substrate will be determined. Initiation and dose escalation will be staggered, such that safety of dose in one patient will be established before subsequent dose escalation. Subjects will have the option to continue to receive weekly treatments with BMN 110 through extension portion of the study until drug is commercially available or study is terminated.

• REC name

  West Midlands - Coventry & Warwickshire Research Ethics Committee

• REC reference

  09/H1211/8

• Date of REC Opinion

  26 Feb 2009

• REC opinion

  Further Information Favourable Opinion