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:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00884949
First received: April 10, 2009
Last updated: July 15, 2011
Last verified: July 2011
  Purpose

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 Intervention Phase
MPS IV A
Drug: BMN 110
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • To evaluate the safety of weekly infusions of BMN 110 based on: vital signs, physical examination, electrocardiogram and echocardiogram tests, cervical spine x-ray, clinical laboratory tests, adverse events, concomitant medications, immunogenicity tests. [ Time Frame: Various, see below for details ] [ Designated as safety issue: Yes ]

    Vital signs, adverse events, concomitant medications: Screening,Baseline, Weeks 1 to 72, and 73 to 84 (as needed).

    Physical examination: Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72

    Electrocardiogram and echocardiogram tests: Screening, Weeks 36, 72

    Cervical spine x-ray: Screening, Week 72

    Clinical laboratory tests: Screening, Baseline, Weeks 3, 6, 11, 15, 18, 23, 27, 30, 35, 48, 60, 72

    Immunogenicity tests: Baseline, Weeks 3, 6, 9, 12, 18, 24, 30, 36, 48, 60, 72



Secondary Outcome Measures:
  • To determine the pharmacokinetic (PK) parameters of infused BMN 110 in subjects with MPS IVA [ Time Frame: Weeks 1, 12, 24, 36 ] [ Designated as safety issue: No ]
  • To determine the pharmacodynamic (PD) parameters of infused BMN 110, as measured by change in KS in subjects with MPS IVA [ 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 ]
  • To evaluate the efficacy of weekly infusions of BMN 110 by monitoring changes in clinical measures as measured by on endurance tests (6MWT, 3MSC), respiratory function tests, anthropometric measurements, and MPS Health Assessment Questionnaire [ Time Frame: Various, see below for details ] [ Designated as safety issue: No ]

    Endurance tests (6MWT, 3MSC): Baseline, Weeks 6, 12, 18, 24, 30, 36, 48, 72

    Respiratory function tests: Baseline, Weeks 12, 24, 36, 48, 72

    Anthropometric measurements: Baseline, Weeks 12, 24, 36, 48, 60, 72

    MPS Health Assessment Questionnaire: Baseline, Weeks 12, 24, 36, 48, 72



Enrollment: 20
Study Start Date: April 2009
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN 110
Within-patient Dose-Escalation
Drug: BMN 110

Subjects will receive a weekly 4-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-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.


  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00884949

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

Additional Information:
No publications provided

Responsible Party: BioMarin Pharmaceutical Inc.
ClinicalTrials.gov Identifier: NCT00884949     History of Changes
Other Study ID Numbers: MOR-002
Study First Received: April 10, 2009
Last Updated: July 15, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

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

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

ClinicalTrials.gov processed this record on April 15, 2014