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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)

Primary Purpose

MPS IV A

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BMN 110 Weekly
Placebo
BMN 110 Every Other Week
Sponsored by
BioMarin Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for MPS IV A focused on measuring Mucopolysaccharidosis IV type A, MPS IV 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

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

BMN 110 Weekly

BMN 110 Every Other Week

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Endurance as Measured by the 6-minute Walk Test

Secondary Outcome Measures

Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine

Full Information

First Posted
January 10, 2011
Last Updated
June 6, 2014
Sponsor
BioMarin Pharmaceutical
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1. Study Identification

Unique Protocol Identification Number
NCT01275066
Brief Title
A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioMarin Pharmaceutical

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MPS IV A
Keywords
Mucopolysaccharidosis IV type A, MPS IV 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
177 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
BMN 110 Weekly
Arm Type
Experimental
Arm Title
BMN 110 Every Other Week
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BMN 110 Weekly
Other Intervention Name(s)
recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
BMN 110 Every Other Week
Other Intervention Name(s)
recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Endurance as Measured by the 6-minute Walk Test
Time Frame
Baseline to Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
Time Frame
Baseline to Week 24
Title
Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine
Time Frame
Baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Debra Lounsbury
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
City
Oakland
State/Province
California
Country
United States
City
Wilmington
State/Province
Delaware
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
New York
State/Province
New York
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Cordoba
Country
Argentina
City
Campina Grande
Country
Brazil
City
Porto Alegre
Country
Brazil
City
Montreal
Country
Canada
City
Sherbrooke
Country
Canada
City
Toronto
Country
Canada
City
Bogota
Country
Colombia
City
Copenhagen
Country
Denmark
City
Lyon
Country
France
City
Paris
Country
France
City
Mainz
Country
Germany
City
Monza
Country
Italy
City
Tokyo
Country
Japan
City
Seoul
Country
Korea, Republic of
City
Amsterdam
Country
Netherlands
City
Coimbra
Country
Portugal
City
Doha
Country
Qatar
City
Riyadh
Country
Saudi Arabia
City
Taipei
Country
Taiwan
City
Birmingham
Country
United Kingdom
City
London
Country
United Kingdom
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25487082
Citation
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.
Results Reference
derived
Links:
URL
http://www.bmrn.com
Description
BioMarin Pharmaceutical Inc. website

Learn more about this trial

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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