Back to resultsLong-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Primary Purpose
Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BMN 110 - Weekly
BMN 110 - Every Other Week
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis 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
Inclusion Criteria:
- Must have completed MOR-004
- Is willing and able to provide written, signed informed consent. Or in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorize representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
- If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
- If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.
Exclusion Criteria:
- Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
- Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
- Was enrolled in a previous BMN 110 study, other than MOR-004.
- Has a 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 pose a safety risk, 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
BMN 110 Weekly
BMN 110 Every Other Week
Arm Description
BMN 110 Weekly: In Part 1, patients will receive an intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
BMN 110 Every Other Week: In Part 1, patients will receive an 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 will receive infusions of placebo on alternating weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in 6-minute Walk (6MW) Test - ITT
Efficacy was assessed by changes from baseline in 6-minute walk test
Change From Baseline in 6-minute Walk (6MW) Test - MPP
Efficacy was assessed by changes from baseline in 6-minute walk test
Secondary Outcome Measures
Change From Baseline in 3-minute Stair Climb Test - ITT
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Change From Baseline in 3-minute Stair Climb Test - MPP
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Change From Baseline in Urine Keratan Sulfate - ITT
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Change From Baseline in Urine Keratan Sulfate - MPP
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01415427
Brief Title
Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Official Title
A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
June 16, 2016 (Actual)
Study Completion Date
June 16, 2016 (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 extension study will evaluate the long-term efficacy and safety of BMN 110 2.0 mg/kg/week and/or BMN 110 2.0 mg/kg/every other week in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).
Detailed Description
This is a multi-center, multinational, extension study to evaluate 2 dose regimens of BMN 110 treatment in patients with MPS IVA who completed MOR-004.
The last study visit assessments for MOR-004 will constitute Baseline for this study. The first study drug dose of this protocol will occur on Week 0 of MOR-005, which is the same as the last visit (Week 24) of MOR-004. Initially, the study will be double-blind with patients previously randomized to BMN 110 in MOR-004 remaining on their assigned BMN 110 dose regimen (qw or qow dosing). The MOR-004 placebo patients will be re-randomized (1:1 ratio) to one of the 2 BMN 110 dose regimen groups: 2.0 mg/kg/qw or 2.0 mg/kg/qow.
There will be two study parts:
Part 1 - randomized double-blind until the optimal BMN 110 dose regimen has been determined, based on the final primary efficacy analysis from MOR-004
Part 2 - open-label BMN 110 treatment with the single optimal dose regimen
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA
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
173 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BMN 110 Weekly
Arm Type
Experimental
Arm Description
BMN 110 Weekly: In Part 1, patients will receive an intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
Arm Title
BMN 110 Every Other Week
Arm Type
Experimental
Arm Description
BMN 110 Every Other Week: In Part 1, patients will receive an 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 will receive infusions of placebo on alternating weeks.
Intervention Type
Drug
Intervention Name(s)
BMN 110 - Weekly
Other Intervention Name(s)
N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT
Intervention Description
In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg/qw administered over a period of approximately 4 hours once a week.
In Part 2, patients will continue to receive 2.0 mg/kg of BMN 110 every week, with no placebo.
Intervention Type
Drug
Intervention Name(s)
BMN 110 - Every Other Week
Other Intervention Name(s)
N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT
Intervention Description
In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week. Patients randomized to the 2.0 mg/kg/qow arm will receive infusions of placebo on alternating weeks, to mask active drug weeks.
In Part 2, patients will receive 2.0 mg/kg of BMN 110 every week, with no placebo.
Primary Outcome Measure Information:
Title
Change From Baseline in 6-minute Walk (6MW) Test - ITT
Description
Efficacy was assessed by changes from baseline in 6-minute walk test
Time Frame
Baseline to week 168
Title
Change From Baseline in 6-minute Walk (6MW) Test - MPP
Description
Efficacy was assessed by changes from baseline in 6-minute walk test
Time Frame
Baseline to week 168
Secondary Outcome Measure Information:
Title
Change From Baseline in 3-minute Stair Climb Test - ITT
Description
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Time Frame
Baseline to week 168
Title
Change From Baseline in 3-minute Stair Climb Test - MPP
Description
Efficacy was assessed by changes from baseline in 3-minute stair climb test.
Time Frame
Baseline to week 168
Title
Change From Baseline in Urine Keratan Sulfate - ITT
Description
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Time Frame
Baseline to week 168
Title
Change From Baseline in Urine Keratan Sulfate - MPP
Description
Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Time Frame
Baseline to week 168
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have completed MOR-004
Is willing and able to provide written, signed informed consent. Or in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorize representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.
Exclusion Criteria:
Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
Was enrolled in a previous BMN 110 study, other than MOR-004.
Has a 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 pose a safety risk, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Debra Lounsbury
Organizational Affiliation
BioMarin Pharmaceutical
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
Oakland
State/Province
California
Country
United States
City
Orange
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
Orlando
State/Province
Florida
Country
United States
City
Honolulu
State/Province
Hawaii
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
Rio de Janeiro
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
Marseille
Country
France
City
Paris
ZIP/Postal Code
Cedex 12
Country
France
City
Paris
ZIP/Postal Code
Cedex 15
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
Oslo
Country
Norway
City
Coimbra
Country
Portugal
City
Lisbon
Country
Portugal
City
Doha
Country
Qatar
City
Riyadh
Country
Saudi Arabia
City
Santiago de Compostela
Country
Spain
City
Taipei
Country
Taiwan
City
Ankara
Country
Turkey
City
Belfast
ZIP/Postal Code
BT9 7AB
Country
United Kingdom
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
City
London
ZIP/Postal Code
NW3 2PF
Country
United Kingdom
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29248359
Citation
Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Mitchell JJ, Burton BK, Guelbert N, Stewart FJ, Hughes DA, Matousek R, Hawley SM, Decker C, Harmatz PR. Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Mol Genet Metab. 2018 Feb;123(2):127-134. doi: 10.1016/j.ymgme.2017.11.015. Epub 2017 Dec 5.
Results Reference
derived
PubMed Identifier
28535791
Citation
Hughes D, Giugliani R, Guffon N, Jones SA, Mengel KE, Parini R, Matousek R, Hawley SM, Quartel A. Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa. Orphanet J Rare Dis. 2017 May 23;12(1):98. doi: 10.1186/s13023-017-0634-0.
Results Reference
derived
PubMed Identifier
27955919
Citation
Long B, Tompkins T, Decker C, Jesaitis L, Khan S, Slasor P, Harmatz P, O'Neill CA, Schweighardt B. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study. Clin Ther. 2017 Jan;39(1):118-129.e3. doi: 10.1016/j.clinthera.2016.11.017. Epub 2016 Dec 10.
Results Reference
derived
Learn more about this trial
Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
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