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

April 10, 2009
April 21, 2009
March 13, 2014
June 30, 2014
June 30, 2014
April 2009
February 2011   (Final data collection date for primary outcome measure)
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.

Safety (Vital signs; Physical examination; Electrocardiogram [ECG]; Echocardiogram; Cervical spine x-ray; Clinical laboratory tests; Immunogenicity tests; Adverse event assessment; Concomitant medications) [ Time Frame: Screening, Baseline, Weeks 1-72 ]
Complete list of historical versions of study NCT00884949 on Archive Site
  • 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.
  • 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.
  • 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%
  • Percent Change From Baseline in MVV [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ]
    Percent Change from baseline in Maximum Voluntary Ventilation.
  • Percent Change From Baseline in FVC [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ]
    Percent Change from baseline in Forced Vital Capacity.
  • Pharmacokinetic (PK) parameters [ Time Frame: Weeks 1, 12, 24, 36 ]
  • Pharmacodynamic (PD) parameters [ Time Frame: Screening, Baseline, Weeks 4, 8, 10, 11, 12, 16, 20, 22, 23, 24, 28, 32, 34, 35, 36, 48, 60, 72 ]
  • Clinical measures [ Time Frame: Baseline, Weeks 6, 12, 18, 24, 30, 36, 48, 60, 72 ]
Not Provided
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A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA
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)
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).
Not Provided
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.

Experimental: BMN 110
Within-patient Dose-Escalation
Intervention: Drug: BMN 110
Hendriksz C, Santra S, Jones SA, Geberhiwot T, Jesaitis L, Long B, Qi Y, Hawley SM, Decker C. Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment. Mol Genet Metab. 2018 Apr;123(4):479-487. doi: 10.1016/j.ymgme.2018.02.011. Epub 2018 Feb 19.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
March 2011
February 2011   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
5 Years to 18 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United Kingdom
Not Provided
Not Provided
BioMarin Pharmaceutical
BioMarin Pharmaceutical
Not Provided
Study Director: Celeste Decker, MD BioMarin Pharmceutical Inc.
BioMarin Pharmaceutical
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP