A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Condition: MPS IV A
MeSH terms: Mucopolysaccharidoses
Intervention: BMN 110 Weekly; Placebo; BMN 110 Every Other Week
Intervention description: BMN 110 Weekly: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.; Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.; BMN 110 Every Other Week: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 177.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No
Keywords: Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; Lysosomal Storage Disorder; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT

Summary:

      This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0
      mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A
      Syndrome).

      There is currently no standard accepted treatment for MPS IVA other than supportive care.
      Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA
      patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular
      uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.

      This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of
      keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and
      heart valve, and reduce the progressive accumulation of KS which is responsible for the
      clinical manifestations of the disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 5 years of age.

          -  Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS
             IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic
             testing confirming diagnosis of MPS IVA.

          -  Willing and able to provide written, signed informed consent, or in the case of
             patients under the age of 18 (or 16 years, depending on the region), provide written
             assent (if required) and written informed consent by a legally authorized
             representative after the nature of the study has been explained, and prior to any
             research-related procedures.

          -  Must meet the study entrance requirements for the 6-minute walk test.

          -  Sexually active patients must be willing to use an acceptable method of contraception
             while participating in the study.

          -  Females of childbearing potential must have a negative pregnancy test at Screening and
             be willing to have additional pregnancy tests during the study.

        Exclusion Criteria:

          -  Previous hematopoietic stem cell transplant (HSCT).

          -  Previous treatment with BMN 110.

          -  Has known hypersensitivity to any of the components of BMN 110.

          -  Major surgery within 3 months prior to study entry or planned major surgery during the
             24-week treatment period.

          -  Pregnant or breastfeeding at Screening or planning to become pregnant (self or
             partner) at any time during the study.

          -  Use of any investigational product or investigational medical device within 30 days
             prior to Screening, or requirement for any investigational agent prior to completion
             of all scheduled study assessments.

          -  Concurrent disease or condition, including but not limited to symptomatic cervical
             spine instability, clinically significant spinal cord compression, or severe cardiac
             disease that would interfere with study participation or safety as determined by the
             Investigator.

          -  Any condition that, in the view of the Investigator, places the patient at high risk
             of poor treatment compliance or of not completing the study.