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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00884949
First received: April 10, 2009
Last updated: May 28, 2014
Last verified: May 2014

April 10, 2009
May 28, 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00884949 on ClinicalTrials.gov Archive Site
  • Change From Baseline in 6MWT [ Time Frame: Baseline to Weeks 12, 24, 36, 48, 72 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Percent Change from baseline in Maximum Voluntary Ventilation.
  • Percent Change From Baseline in FVC [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ] [ Designated as safety issue: No ]
    Percent Change from baseline in Forced Vital Capacity.
  • Pharmacokinetic (PK) parameters [ Time Frame: Weeks 1, 12, 24, 36 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Clinical measures [ Time Frame: Baseline, Weeks 6, 12, 18, 24, 30, 36, 48, 60, 72 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
MPS IV A
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
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.
Both
5 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00884949
MOR-002
No
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