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Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

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ClinicalTrials.gov Identifier: NCT01415427
Recruitment Status : Completed
First Posted : August 12, 2011
Results First Posted : May 19, 2017
Last Update Posted : May 19, 2017
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Tracking Information
First Submitted Date  ICMJE August 8, 2011
First Posted Date  ICMJE August 12, 2011
Results First Submitted Date  ICMJE April 13, 2017
Results First Posted Date  ICMJE May 19, 2017
Last Update Posted Date May 19, 2017
Study Start Date  ICMJE July 2011
Actual Primary Completion Date June 16, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • Change From Baseline in 6-minute Walk (6MW) Test - ITT [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in 6-minute walk test
  • Change From Baseline in 6-minute Walk (6MW) Test - MPP [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in 6-minute walk test
Original Primary Outcome Measures  ICMJE
 (submitted: August 11, 2011)
Primary Long-Term Safety/Efficacy Evaluation [ Time Frame: Approximately 240 weeks ]
To evaluate the long-term safety and efficacy of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow in patients with MPS IVA. Safety results will be determined by numbers and severity of adverse events as well as descriptive statistic analysis of other safety related assessments. Efficacy will be assessed by changes from baseline in 6-minute walk test and 3-minute stair climb test as well as urine KS concentrations.
Change History Complete list of historical versions of study NCT01415427 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • Change From Baseline in 3-minute Stair Climb Test - ITT [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in 3-minute stair climb test.
  • Change From Baseline in 3-minute Stair Climb Test - MPP [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in 3-minute stair climb test.
  • Change From Baseline in Urine Keratan Sulfate - ITT [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
  • Change From Baseline in Urine Keratan Sulfate - MPP [ Time Frame: Baseline to week 168 ]
    Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 11, 2011)
Long-Term evaluation of changes in biochemical markers of inflammation and bone and cartilage metabolism [ Time Frame: Approximately 240 weeks ]
To evaluate the long-term effect of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow on changes in biochemical markers of inflammation and bone and cartilage metabolism, in patients with MPS IVA.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Official Title  ICMJE A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
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
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
  • Mucopolysaccharidosis IV A
  • Morquio A Syndrome
  • MPS IVA
Intervention  ICMJE
  • Drug: BMN 110 - Weekly

    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.

    Other Names:
    • N-acetylgalactosamine-6-sulfatase
    • N-acetylgalactosamine-6-sulfate sulfatase
    • galactose-6-sulfatase
    • GALNS
    • enzyme replacement therapy
    • ERT
  • Drug: BMN 110 - Every Other Week

    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.

    Other Names:
    • N-acetylgalactosamine-6-sulfatase
    • N-acetylgalactosamine-6-sulfate sulfatase
    • galactose-6-sulfatase
    • GALNS
    • enzyme replacement therapy
    • ERT
Study Arms  ICMJE
  • Experimental: BMN 110 Weekly
    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.
    Intervention: Drug: BMN 110 - Weekly
  • Experimental: BMN 110 Every Other 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.
    Intervention: Drug: BMN 110 - Every Other Week
Publications *

*   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: April 22, 2014)
173
Original Estimated Enrollment  ICMJE
 (submitted: August 11, 2011)
162
Actual Study Completion Date  ICMJE June 16, 2016
Actual Primary Completion Date June 16, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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,   Norway,   Portugal,   Qatar,   Saudi Arabia,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01415427
Other Study ID Numbers  ICMJE MOR-005
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 April 2017

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