Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome
Condition: Mucopolysaccharidosis IVA; Morquio A Syndrome; MPS IVA
MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis IV; Syndrome
Intervention: BMN 110; BMN 110
Intervention description: Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 192 weeks.; Weekly IV infusions of BMN 110 at 4.0 mg/kg/week over a period of approximately 4 hours per infusion for 27 weeks, and will eventually transition to 2.0 mg/kg/week for up to an additional 166 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: No
Keywords: Mucopolysaccharidosis IVA Type A; MPS IVA 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; MOR-008; CPET; MST; muscle strength test; physiological effect

Summary:

      The primary objective of this study was to evaluate the safety of a 2.0 mg/kg/week and a 4.0
      mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary
      objectives were to investigate the effect of the two doses on exercise capacity for up to 196
      weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 was
      assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is willing and able to provide written, signed informed consent (or patient's legally
             authorized representative) after the nature of the study has been explained and prior
             to performance of any research- related procedure. Also, patients who do not meet
             country and local age requirements for informed consent must be willing and able to
             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 performance of any research-related procedure.

          -  Has documented clinical diagnosis of Morquio A Syndrome (MPS IVA) based on clinical
             signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte
             N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or genetic testing
             confirming diagnosis of MPS IVA.

          -  Is at least 7 years of age

          -  Is able to walk ≥ 200 meters as assessed by the 6-minute Walk Test (6MWT)

          -  If sexually active, is willing to use an acceptable method of contraception while
             participating in the study

          -  If female of childbearing potential, must have a negative pregnancy test at the
             Screening Visit and be willing to have additional pregnancy tests during the study

          -  Is willing and able to perform all study procedures, including cardiopulmonary
             exercise testing (CPET)

        Exclusion Criteria:

          -  Inability to perform an exercise test due to limited mobility

          -  Body weight greater than 95 kg at Screening

          -  Severe, untreated sleep apnea as measured during Screening with a home sleep testing
             device

          -  Patients with a history of, or current condition of sleep apnea or sleep disordered
             breathing under adequate treatment may be enrolled if approved by the medical monitor.

          -  Requirement for supplemental oxygen

          -  Use of ventilator assistance in the 3 months prior to study entry

          -  Use of positive airway pressure (continuous positive airway pressure, CPAP, or bilevel
             airway pressure) for treatment of sleep apnea or sleep disordered breathing is allowed
             if settings have been stable for at least 1 month prior to study entry, and is
             approved by the medical monitor.

          -  Has a 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 pose a safety risk,
             as determined by the Investigator

          -  Has previous hematopoietic stem cell transplant (HSCT)

          -  Has received previous treatment with BMN 110

          -  Has a known hypersensitivity to BMN 110 or its excipients

          -  Has had major surgery within 3 months prior to study entry or is planning to have a
             major surgery during the duration of the study

          -  Use of any other investigational product (IP) or investigational medical device within
             30 days prior to the beginning of the Screening Period or requires any investigational
             agent prior to completion of all scheduled study assessments

          -  Is pregnant or breastfeeding during the Screening Period or planning to become
             pregnant (self or partner) at any time during the study

          -  Has a concurrent disease or condition that may interfere with study participation or
             safety, and/or ability to perform study procedures as determined by the Investigator

          -  Has any condition that, in the view of the Investigator, poses a safety risk to the
             patient

          -  Has 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