Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome

A Randomized, Double-Blind, Pilot Study of the Safety and Physiological Effects of Two Doses of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

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.

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