A Multicenter, Multinational, Observational Morquio A Registry Study (MARS)

Study Overview
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Brief Summary
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The objectives of this program are: to characterize and describe the Mucopolysaccharidosis IV type A (MPS IVA) population as a whole, including the heterogeneity, progression, and natural history of MPS IVA; to evaluate the long-term effectiveness and safety of Vimizim®, including, but not limited to, the occurrence of serious hypersensitivity reactions, anaphylaxis, and changes in antibody status; to help the medical community with the development of recommendations for monitoring MPS IVA patients and reports on patient outcomes to optimize patient care; to collect data on other treatment paradigms, and evaluate the prevalences of their use and their effectiveness; to characterize the effects and safety of Vimizim treatment 5 years from enrollment in the Registry for patients under 5 years of age; to monitor pregnancy exposure, including maternal, neonatal, and infant outcomes; and to monitor patients who have completed the MOR-005 and MOR-007 clinical trials. These patients will be encouraged to enroll in the applicable Registry Substudy and will be monitored using the MOR-005 and MOR-007 assessment schedules, respectively.

Detailed Description
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MARS is a multicenter, multinational, observational disease registry for patients diagnosed with Mucopolysaccharidosis Type IVA (MPS IVA). The Registry will collect medical history, and clinical and safety assessments every six months, for up to 10 years. The Registry will enroll and collect data on patients over a period of at least 8 years from the time of the first marketing approval globally and data on individual patients will continue to be collected for at least 2 years from the time the last patient was enrolled or until the Registry is completed. These assessments are designed to further characterize the spectrum of clinical signs and symptoms of the disease, and to further characterize the safety profile of Vimizim in a broader population. It is not required that patients receive Vimizim to be eligible to participate in this Registry. In addition, this Registry will collect additional data on patients who have completed the MOR-005 and MOR-007 clinical trials. The MOR-005 and MOR-007 clinical trial patients will be enrolled into the appropriate Registry Substudy for a minimum of 5 years from the time of the patient's enrollment in the MOR-005 clinical study or MOR-007 clinical study. After the 5 year period, these patients should remain in MARS until the Registry is complete.

Official Title
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A Multicenter, Multinational, Observational Morquio A Registry Study (MARS)

Conditions
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Mucopolysaccharidosis IV Type A, Morquio A Syndrome, MPS IVA

Intervention / Treatment
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* Drug: Vimizim® (elosulfase alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients eligible to participate in this Registry must meet all of the following criteria: Diagnosed with MPS IVA as confirmed by either N-acetylgalactosamine 6-sulfatase (GALNS) enzymatic test or by a diagnostic molecular test Willing and able to provide written, signed informed consent, or, in the case of patients age < 18 years, provide written assent (if required) and written informed consent, signed by a legally authorized representative after the nature of the Registry has been explained and prior to performance of any Registry-related procedures Willing to undergo assessments to establish baseline data or permit Investigator to enter assessment data recorded prior to Registry entry if available in the patient's medical records. Entry assessments may include: demographics, medical history, urinary keratan sulfate level, urinary protein level, immunogenicity testing, vital signs, physical examination, and height and weight Patients eligible to participate in the Registry Substudy for MOR-005 must meet all of the following criteria: Must have completed the MOR-005 clinical trial Willing and able to provide written, signed informed consent, or, in the case of patients age < 18 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the Registry Substudy has been explained and prior to any Registry-related Substudy procedures Willing to permit Investigator to enter assessment data recorded prior to Registry Substudy entry if available in the patient's medical records Patients eligible to participate in this Registry Substudy for MOR-007 must meet all of the following criteria: Must have completed the MOR-007 clinical trial Willing and able to provide written, signed informed consent, or in the case of patients age < 18 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the Registry Substudy has been explained, and prior to any Registry-related Substudy procedures Willing to permit Investigator to enter assessment data recorded prior to Registry Substudy entry if available in the patient's medical records Exclusion Criteria: Patients who meet the following exclusion criterion will not be eligible to participate in the Registry or Registry Substudies: • Patients currently participating in a BMN 110 (elosulfase alfa) clinical trial
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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Vimizim® (elosulfase alfa)|Recombinant human N acetylgalactosamine 6 sulfatase (rhGALNS)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Vimizim treated patients as measured by the incidences of Adverse Events, Serious Adverse Events, and immunology tests | Additional safety measures are medications, occurrence of Bone Marrow Transplant/Hematopoietic Stem Cell Transplant, clinical laboratory tests, vital signs, Electrocardiograms, Echocardiograms, immunogenicity results, physical examinations, imaging studies, and cervical spine imaging. All assessments in this observational study will be carried out per the participating institution's standard of care. The MARS Annual report will descriptively summarize the safety and outcome measurements for the duration of this voluntary, observational study. | 10 Years | 
| Efficacy of Vimizim as measured by the 6MWT, 3MSCT, RFTs, FEV1, FIVC, FVC, and MVV | Efficacy of Vimizim as measured by the changes in the 6 minute walk test (6MWT), 3 minute stir climb test (3MSCT), respiratory function tests (RFTs) including forced expiratory volume for 1 second (FEV1), forced inspiratory vital capacity (FIVC), forced vital capacity (FVC), and maximum voluntary ventilation (MVV) and by urinary Keratan Sulfate. | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The MARS Pregnancy Substudy will collect safety data measured by Adverse Events, Serious Adverse Events, immunology tests, and the infant outcomes as measured by a live birth | The MARS Pregnancy Substudy will collect safety data on the outcomes of pregnancy in women who receive Vimizim as measured by Adverse Events, Serious Adverse Events, immunology tests, and the infant outcomes as measured by a live birth. | 10 years |