A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00884949
Recruitment Status : Completed
First Posted : April 21, 2009
Results First Posted : June 30, 2014
Last Update Posted : June 30, 2014
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief Summary:
This multicenter, open-label study is designed to assess safety, dose-response using pharmacokinetic (PK) and pharmacodynamic (PD) measures, and clinical efficacy of BMN 110 in subjects between 5 and 18 years of age, diagnosed with Mucopolysaccharidosis IVA (MPS IVA).

Condition or disease Intervention/treatment Phase
MPS IV A Drug: BMN 110 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multicenter, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)
Study Start Date : April 2009
Actual Primary Completion Date : February 2011
Actual Study Completion Date : March 2011

Arm Intervention/treatment
Experimental: BMN 110
Within-patient Dose-Escalation
Drug: BMN 110

Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen:

  • Weeks 1-12: 0.1 mg/kg/week
  • Weeks 13-24: 1.0 mg/kg/week
  • Weeks 25-36: 2.0 mg/kg/week

Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.

Primary Outcome Measures :
  1. Subject Incidence of Treatment Emergent AEs [ Time Frame: Entire Study, through week 84 ]

    The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA.

    The safety variable incidence of TEAE is summarized.

Secondary Outcome Measures :
  1. Change From Baseline in 6MWT [ Time Frame: Baseline to Weeks 12, 24, 36, 48, 72 ]
    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.

  2. Change From Baseline in 3MSCT [ Time Frame: Baseline to Weeks 12, 24, 36, 48, 72 ]
    Change from baseline in the 3-minute Stair Climb Test. 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.

  3. Percent Change From Baseline in uKS [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ]
    Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%

  4. Percent Change From Baseline in MVV [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ]
    Percent Change from baseline in Maximum Voluntary Ventilation.

  5. Percent Change From Baseline in FVC [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ]
    Percent Change from baseline in Forced Vital Capacity.

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA.
  • Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, 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.
  • Between 5 and 18 years of age, inclusive.
  • Sexually active subjects 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 Screening and be willing to have additional pregnancy tests during the study.
  • Willing to perform all study procedures as physically possible.

Exclusion Criteria:

  • Previous hematopoietic stem cell transplant (HSCT).
  • Has known hypersensitivity to BMN 110 or its excipients.
  • Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
  • Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • Concurrent disease or condition that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability.
  • Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00884949

United Kingdom
Birmingham, United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Study Director: Celeste Decker, MD BioMarin Pharmceutical Inc.

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: BioMarin Pharmaceutical Identifier: NCT00884949     History of Changes
Other Study ID Numbers: MOR-002
First Posted: April 21, 2009    Key Record Dates
Results First Posted: June 30, 2014
Last Update Posted: June 30, 2014
Last Verified: May 2014

Keywords provided by BioMarin Pharmaceutical:
Mucopolysaccharidosis IV type A
Mucopolysaccharidosis IVA
Morquio A Syndrome
Lysosomal Storage Disorder
N-acetylgalactosamine-6-sulfate sulfatase
enzyme replacement therapy

Additional relevant MeSH terms:
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases