Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01697319
First received: September 17, 2012
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.


Condition Intervention Phase
Mucopolysaccharidosis IVA
Morquio A Syndrome
MPS IVA
Drug: BMN 110
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Efficacy will be determined/summarized by percent changes of the domain scores for upper extremity function, dexterity, mobility, pain, and self-care and functional ability testing from baseline. [ Time Frame: Up to 144 weeks ] [ Designated as safety issue: No ]
    • Upper extremity function will be tested using the Grip-Pinch Test.
    • Dexterity will be tested using the Functional Dexterity Test.
    • Mobility will be tested using the 25 Foot Walk test
    • Pain will be determined by the Brief Pain Inventory-Short Form questionnaire or the Adolescent Pediatric Pain Tool
    • Functional/self care abilities will be determined using Pediatric Outcomes Data Collection Instrument (PODCI)or the SF-36 questionnaire.

    Efficacy will be measured at the following timepoints: Baseline, Weeks: 12, 24, 36, 48, 72, 96, 120, 144 / ETV. Weeks: 60, 84, 108, & 132 (Pain Inventory & PODCI only.)



Secondary Outcome Measures:
  • Change in respiratory function using a summarized analysis of the percentage change in FET, FIVC, FVC, FEV1, MVV and optional TLC values from the Baseline visit. [ Time Frame: Up to 144 weeks ] [ Designated as safety issue: No ]
    Timepoints: Baseline, Weeks: 24, 48, 96, 144 / ETV

  • Change in urinary KS over time as determined by descriptive statistics. [ Time Frame: Up to 144 weeks ] [ Designated as safety issue: No ]
    Timepoints: Baseline, Weeks: 2, 4, 6, 12, 24, 36, 48, 72, 96, 120, 144 / ETV

  • Assessment of effect on sleep apnea results as calculated using the Apnea-hypopnea index(AHI). [ Time Frame: Up to 144 weeks ] [ Designated as safety issue: No ]
    A subset consisting of any subjects who have abnormal overnight pulse oximetry readings will be assessed for sleep apnea. Only selected sites are participating in the sleep apnea study.


Other Outcome Measures:
  • Descriptive summary of clinical safety assessments [ Time Frame: Continuously for up to 144 weeks or more ] [ Designated as safety issue: Yes ]
    Incidence of AEs and changes in neurologic examinations, vital signs, ECHOs, ECGs, cervical spine radiographs, immunogenicity tests, clinical laboratory tests, and concomitant medications.


Enrollment: 15
Study Start Date: August 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN 110 at 2.0 mg/kg/week
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.
Drug: BMN 110
Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.
Other Names:
  • N-acetylgalactosamine-6-sulfatase
  • N-acetylgalactosamine-6-sulfate
  • sulfatase
  • galactose-6-sulfatase
  • GALNS
  • enzyme replacement therapy
  • ERT

Detailed Description:

Effect is defined by the following domains:

  • Upper extremity function and dexterity
  • Mobility
  • Pain
  • Self care and functional abilities
  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
  • Has documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
  • Is ≥ 5 years of age.
  • If sexually active, is willing to use an acceptable method of contraception while participating in the study.
  • Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
  • Is willing and able to perform all study procedures as physically possible.

Exclusion Criteria:

  • Is able to walk farther than a specified distance as assessed by the 6MWT.
  • Has previous hematopoietic stem cell transplant (HSCT).
  • Has received previous treatment with BMN 110.
  • Has a known hypersensitivity to any of the components of BMN 110.
  • Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study.
  • Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments.
  • Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
  • Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety as determined by the Investigator.
  • Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01697319

Locations
United States, California
Children's Hospital & Research Center Oakland
Oakland, California, United States
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Germany
Universitätsklinikum Hamburg
Hamburg, Germany
University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica
Mainz, Germany
United Kingdom
NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital
Birmingham, United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
Manchester, United Kingdom
Salford Royal NHS Foundation Trust
Salford, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Celeste Decker, M.D. BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01697319     History of Changes
Other Study ID Numbers: MOR-006, 2011-005703-33
Study First Received: September 17, 2012
Last Updated: December 20, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ethics Commission
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by BioMarin Pharmaceutical:
Mucopolysaccharidosis IVA Type A
MPS IVA Type A
Mucopolysaccharidosis IVA
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
MOR-006
CPET
Limited ambulation
Grip/ Pinch

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 August 20, 2014