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

Completed

• Conditions: Mucopolysaccharidosis IV Type A; MPS IVA; Morquio A Syndrome

• Registration Number: NCT02294877
• Lead Sponsor: BioMarin Pharmaceutical

Brief Summary

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

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 Timeline

• Study Start: 2014-09
• Study First Submitted: 2014-10-28
• Study First Submitted QC: 2014-11-17
• Study First Posted: 2014-11-19
• Primary Completion: 2024-02-21
• Study Completion: 2024-02-21
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 418

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety of Vimizim treated patients as measured by the incidences of Adverse Events, Serious Adverse Events, and immunology tests	10 Years	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.
Efficacy of Vimizim as measured by the 6MWT, 3MSCT, RFTs, FEV1, FIVC, FVC, and MVV	10 years	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.

Secondary Outcome Measures

Name	Time	Method
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	10 years	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.

Trial Locations

Locations (79)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Ann & Robert H. Lurie Children's Hospital; 🇺🇸 Chicago, Illinois, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Children's National Health System; 🇺🇸 Washington, District of Columbia, United States

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

A.I. Dupont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Emory University; 🇺🇸 Decatur, Georgia, United States

Children's Hospital of Boston; 🇺🇸 Boston, Massachusetts, United States

University of Louisville Research Foundation Inc. - Kosair Charities Pediatric Clinical Research Unit; 🇺🇸 Louisville, Kentucky, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Atlantic Health System; 🇺🇸 Morristown, New Jersey, United States

University Of Iowa; 🇺🇸 Iowa City, Iowa, United States

Children's Hospital of the King's Daughters; 🇺🇸 Norfolk, Virginia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

UTHealth McGovern Medical School; 🇺🇸 Houston, Texas, United States

NYU-Langone Medical Center School of Medicine; 🇺🇸 New York, New York, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Universitätsklinik Graz; 🇦🇹 Graz, Austria

Medical University of Vienna; 🇦🇹 Vienna, Austria

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Antwerp University Hospital; 🇧🇪 Edegem, Belgium

Adult Metabolic Diseases Clinic Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Perth Children's Hospital; 🇦🇺 Perth, Nedlands, Australia

Children's Hospital of Westmead; 🇦🇺 Westmead, New South Wales, Australia

Children's Hospital of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Children's Health Queensland Hospital and Health Service; 🇦🇺 South Brisbane, Queensland, Australia

Royal Children's Hospital - Victoria; 🇦🇺 Parkville, Victoria, Australia

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Sainte-Justine Hospital; 🇨🇦 Montreal, Quebec, Canada

Children's & Women's Centre of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

Université de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

Copenhagen University Hospital, Klinik For Sjaeldne Handicap; 🇩🇰 Copenhagen, Dk-2100, Denmark

Klinika Dětského a Dorostového Lékařstvi; 🇨🇿 Prague, Czechia

Hôpital Femme Mère Enfant; 🇫🇷 Bron Cedex, France

Hospital Necker; 🇫🇷 Paris Cedex 15, France

Hopital d'enfants - Hopitaux de Brabois; 🇫🇷 Vandœuvre-lès-Nancy, France

Temple Street Children's University Hospital; 🇮🇪 Dublin, Ireland

Azienda Policlinico Vittorio Emanuele, presidio G Rodolico, Università di Catania; 🇮🇹 Catania, Italy

Azienda Ospedaliero Meyer; 🇮🇹 Firenze, Italy

Azienda Ospedaliero San Gerardo di Monza; 🇮🇹 Monza, Italy

Federico II University Hospital; 🇮🇹 Naples, Italy

Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

University of Malay Medical Center; 🇲🇾 Kuala Lumpur, Malaysia

Academic Medical Center - University of Amsterdam; 🇳🇱 Amsterdam, Netherlands

Rotterdam University Hospital Medical Centre; 🇳🇱 Rotterdam, Netherlands

Hospital Pediátrico de Coimbra (Centro Hospitalar de Coimbra); 🇵🇹 Coimbra, Portugal

Centro Hospitalar Lisboa Centro - Hospital de Dona Estefânia; 🇵🇹 Lisbon, Portugal

San Jorge Children's Hospital, Centro de Investigaciones Clinicas; 🇵🇷 San Juan, Puerto Rico

The Children Memorial Health Institute; 🇵🇱 Warszawa, Poland

Centro Hospitalar Lisboa Norte; 🇵🇹 Lisboa, Portugal

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taoyuan County, Taiwan

Changhua Christian Hospital (CCH); 🇨🇳 Changhua City, Changhua County, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, San-Min District, Taiwan

Chang Gung Memorial Hospital Kaohsiung Branch; 🇨🇳 Kaohsiung City, Taiwan

Kaohsiung Veterans General Hospital; 🇨🇳 Kaohsiung, Taiwan

China Medical University and Hospital; 🇨🇳 Taichung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng Kung University (NCKU) Hospital; 🇨🇳 Tainan, Taiwan

Birmingham Children's Hospital; 🇬🇧 Birmingham, United Kingdom

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

MacKay Memorial Hospital; 🇨🇳 Taipei, Taiwan

University Hospital Birmingham - Selly Oaks; 🇬🇧 Birmingham, United Kingdom

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Royal Free NHS Foundation Trust; 🇬🇧 London, United Kingdom

National Hospital for Neurology and Neurosurgery; 🇬🇧 London, United Kingdom

Great Ormond Street Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

Salford Royal NHS Foundation Trust; 🇬🇧 Salford, United Kingdom

Royal Manchester Children's Hospital - Manchester University NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Miami Children's Hospital; 🇺🇸 Miami, Florida, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Children's Hospitals and Clinics of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Children's Specialty Center of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States