A Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Study Overview
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Brief Summary
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This multicenter, open-label extension study is designed to assess long-term efficacy and safety of 2.0 milligrams (mg)/kilogram(kg)/week of BMN 110 in patients diagnosed with Mucopolysaccharidosis IVA (MPS IVA). Patients with MPS IVA, who enrolled in a prior BioMarin sponsored clinical study of BMN 110 (NCT00884949; Study Identification Number MOR-002), were eligible to enroll in this study (except patients who enrolled in NCT01275066; Study Identification Number MOR-004).

Official Title
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A Multicenter, Multinational, Open-Label, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Conditions
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MPS IV A, Mucopolysaccharidosis IVA, Morquio A Syndrome

Intervention / Treatment
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* Drug: BMN 110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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 Baseline and be willing to have additional pregnancy tests during the study. Must have enrolled in a prior BioMarin sponsored clinical study of BMN 110. Exclusion Criteria: Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study. Use of any investigational product (other than BMN 110 in a prior clinical study) or investigational medical device within 30 days prior to Baseline, 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. Were enrolled in MOR-004 (patients from MOR-004 may be eligible to participate in a separate, appropriately designed, extension study).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMN 110<br> | Drug: BMN 110<br>* Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Evaluation | The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section. | Entire Study Period, up to 240 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Endurance as Measured by the 6-minute Walk Test During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). | Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes. | Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial | 
| Change in Baseline in Endurance as Measured by the 3 Minute Stair Climb During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). | Change from baseline in the 3-minute Stair Climb Test (3MSCT). Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute. | Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial | 
| Percent Change From Baseline in Urine Keratan Sulfate (uKS) Levels During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). | Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100% | Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 168 weeks during the MOR-100 extension trial | 
| Percent Change From Baseline in Respiratory Function Test MVV During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). | Percent Change from baseline in Maximum Voluntary Ventilation. | Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial | 
| Percent Change From Baseline in Respiratory Function Test FVC During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). | Percent Change from baseline in Forced Vital Capacity. | Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LSD, Mucopolysaccharidosis IV type A, MPS IV Type A, Mucopolysaccharidosis IVA, MPS IVA, Morquio A Syndrome, Lysosomal Storage Disorder, N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT