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

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.

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis IV Type A; Morquio A Syndrome; MPS IVA
• Intervention / Treatment: Drug: Vimizim® (elosulfase alfa)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 418

Contacts and Locations

Study Locations

• Australia
  • Nedlands
    • Perth, Nedlands, Australia, 6009
      • Perth Children's Hospital
  • New South Wales
    • Westmead, New South Wales, Australia
      • Westmead Hospital
    • Westmead, New South Wales, Australia, 2145
      • Children's Hospital of Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Children's Health Queensland Hospital and Health Service
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital - Victoria
  • Western Australia
    • Perth, Western Australia, Australia, 6847
      • Royal Perth Hospital
• Austria
  • Graz, Austria, 8036
    • Universitätsklinik Graz
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Adult Metabolic Diseases Clinic Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Children's & Women's Centre of British Columbia
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H3T 1C5
      • Sainte-Justine Hospital
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Université de Sherbrooke
• Czechia
  • Prague, Czechia, 12000
    • Klinika Dětského a Dorostového Lékařstvi
• Denmark
  • Dk-2100
    • Copenhagen, Dk-2100, Denmark
      • Copenhagen University Hospital, Klinik For Sjaeldne Handicap
• France
  • Bron Cedex, France, 69677
    • Hôpital Femme Mère Enfant
  • Paris Cedex 15, France, 75743
    • Hospital Necker
  • Vandœuvre-lès-Nancy, France, 54500
    • Hopital d'enfants - Hopitaux de Brabois
• Ireland
  • Dublin, Ireland
    • Temple Street Children's University Hospital
• Italy
  • Catania, Italy, 95125
    • Azienda Policlinico Vittorio Emanuele, presidio G Rodolico, Università di Catania
  • Firenze, Italy, 50139
    • Azienda Ospedaliero Meyer
  • Monza, Italy, 20090
    • Azienda Ospedaliero San Gerardo di Monza
  • Naples, Italy, 80131
    • Federico II University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuala Lumpur, Malaysia
    • University of Malay Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center - University of Amsterdam
  • Rotterdam, Netherlands, 3015 GE
    • Rotterdam University Hospital Medical Centre
• Poland
  • Warszawa, Poland, 04-730
    • The Children Memorial Health Institute
• Portugal
  • Coimbra, Portugal, 3000-062
    • Hospital Pediátrico de Coimbra (Centro Hospitalar de Coimbra)
  • Lisboa, Portugal
    • Centro Hospitalar Lisboa Norte
  • Lisbon, Portugal, 1169-045
    • Centro Hospitalar Lisboa Centro - Hospital de Dona Estefânia
• Puerto Rico
  • San Juan, Puerto Rico, 00912
    • San Jorge Children's Hospital, Centro de Investigaciones Clinicas
• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Kaohsiung Veterans General Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Memorial Hospital Kaohsiung Branch
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 40402
    • China Medical University and Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University (NCKU) Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 10050
    • National Taiwan University Hospital
  • Changhua County
    • Changhua City, Changhua County, Taiwan, 50006
      • Changhua Christian Hospital (CCH)
  • San-Min District
    • Kaohsiung, San-Min District, Taiwan, 80756
      • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taoyuan County
    • Taoyuan City, Taoyuan County, Taiwan, 33305
      • Chang Gung Memorial Hospital
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Birmingham, United Kingdom, B15 2WB
    • University Hospital Birmingham - Selly Oaks
  • London, United Kingdom, WC1N 3BG
    • National Hospital For Neurology and Neurosurgery
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Royal Free NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital - Manchester University NHS Foundation Trust
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • A.I. Dupont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52524
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Research Foundation Inc. - Kosair Charities Pediatric Clinical Research Unit
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital of Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Children's Specialty Center of Nevada
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • New York, New York, United States, 10016
      • NYU-Langone Medical Center School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • UTHealth McGovern Medical School
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98145-5005
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with MPS IVA disease and patients treated with Vimizim, although patients are not required to receive Vimizim to be eligible to participate in this Registry.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Collaborators: ICON plc
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 21, 2024
• Study Completion (Actual): February 21, 2024

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimated): November 19, 2014

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Mucopolysaccharidoses; Osteochondrodysplasias; Mucopolysaccharidosis IV
• Other Study ID Numbers: 110-504

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO