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A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

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ClinicalTrials.gov Identifier: NCT01275066
Recruitment Status : Completed
First Posted : January 12, 2011
Results First Posted : April 15, 2014
Last Update Posted : July 7, 2014
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE January 10, 2011
First Posted Date  ICMJE January 12, 2011
Results First Submitted Date  ICMJE March 11, 2014
Results First Posted Date  ICMJE April 15, 2014
Last Update Posted Date July 7, 2014
Study Start Date  ICMJE February 2011
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2014)
Change From Baseline in Endurance as Measured by the 6-minute Walk Test [ Time Frame: Baseline to Week 24 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2011)
Change from baseline in endurance as measured by the 6-minute Walk Test [ Time Frame: Screening and every 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2014)
  • Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test [ Time Frame: Baseline to Week 24 ]
  • Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine [ Time Frame: Baseline to Week 24 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2011)
  • Change from baseline in endurance as measured by the 3-minute Stair-Climb Test [ Time Frame: Screening and every 12 weeks ]
  • Change from baseline in urine keratan sulfate (KS) levels (normalized to creatinine) [ Time Frame: Baseline, week 2, 4, 8, 12, 16, 20, and 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Official Title  ICMJE A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multinational Clinical Study to Evaluate the Efficacy and Safety of 2.0 mg/kg/Week and 2.0 mg/kg/Every Other Week BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Brief Summary

This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

There is currently no standard accepted treatment for MPS IVA other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.

This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and heart valve, and reduce the progressive accumulation of KS which is responsible for the clinical manifestations of the disorders.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE MPS IV A
Intervention  ICMJE
  • Drug: BMN 110 Weekly
    BMN 110 Weekly: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
    Other Names:
    • recombinant human N-acetylgalactosamine-6-sulfatase
    • rhGALNS
  • Drug: Placebo
    Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.
  • Drug: BMN 110 Every Other Week
    BMN 110 Every Other Week: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.
    Other Names:
    • recombinant human N-acetylgalactosamine-6-sulfatase
    • rhGALNS
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: BMN 110 Weekly
    Intervention: Drug: BMN 110 Weekly
  • Experimental: BMN 110 Every Other Week
    Intervention: Drug: BMN 110 Every Other Week
Publications * Schweighardt B, Tompkins T, Lau K, Jesaitis L, Qi Y, Musson DG, Farmer P, Haller C, Shaywitz AJ, Yang K, O'Neill CA. Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients With Morquio A Syndrome: Results From MOR-004, a Phase III Trial. Clin Ther. 2015 May 1;37(5):1012-1021.e6. doi: 10.1016/j.clinthera.2014.11.005. Epub 2014 Dec 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 2, 2013)
177
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2011)
162
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • At least 5 years of age.
  • 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.
  • Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), 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.
  • Must meet the study entrance requirements for the 6-minute walk test.
  • Sexually active patients 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.

Exclusion Criteria:

  • Previous hematopoietic stem cell transplant (HSCT).
  • Previous treatment with BMN 110.
  • Has known hypersensitivity to any of the components of BMN 110.
  • Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.
  • 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, including but not limited to symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation or safety as determined by the Investigator.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   Colombia,   Denmark,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Portugal,   Qatar,   Saudi Arabia,   Taiwan,   United Kingdom,   United States
Removed Location Countries Australia,   Norway,   Poland,   Switzerland,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01275066
Other Study ID Numbers  ICMJE MOR-004
2010-020198-18 ( EudraCT Number )
10/H1306/87 ( Other Identifier: National Research Ethics Service )
18972/0213/001-0001 ( Other Identifier: Medicines and Healthcare Products Regulatory Agency )
2011_038#B201129 ( Other Identifier: Medical Ethics Review Committee (METC) )
145240 ( Other Identifier: Health Canada )
2011-01-09 ( Other Identifier: Committee for the Protection of Personnes )
20110012889 ( Other Identifier: Korean Food & Drug Administration (KFDA) )
0999935174 ( Other Identifier: Taiwan FDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioMarin Pharmaceutical
Study Sponsor  ICMJE BioMarin Pharmaceutical
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Debra Lounsbury BioMarin Pharmaceutical
PRS Account BioMarin Pharmaceutical
Verification Date June 2014

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