NCT01275066

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
177

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Feb 2011

Geographic Reach
17 countries

28 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 10, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 12, 2011

Completed
20 days until next milestone

Study Start

First participant enrolled

February 1, 2011

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2012

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

April 15, 2014

Completed
Last Updated

July 7, 2014

Status Verified

June 1, 2014

Enrollment Period

1.5 years

First QC Date

January 10, 2011

Results QC Date

March 11, 2014

Last Update Submit

June 6, 2014

Conditions

Keywords

Mucopolysaccharidosis IV type AMPS IV Type AMucopolysaccharidosis IVAMPS IVAMorquio A SyndromeLysosomal Storage DisorderLSDN-acetylgalactosamine-6-sulfataseN-acetylgalactosamine-6-sulfate sulfatasegalactose-6-sulfataseGALNSenzyme replacement therapyERT

Outcome Measures

Primary Outcomes (1)

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

    Baseline to Week 24

Secondary Outcomes (2)

  • Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test

    Baseline to Week 24

  • Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine

    Baseline to Week 24

Study Arms (3)

Placebo

PLACEBO COMPARATOR
Drug: Placebo

BMN 110 Weekly

EXPERIMENTAL
Drug: BMN 110 Weekly

BMN 110 Every Other Week

EXPERIMENTAL
Drug: BMN 110 Every Other Week

Interventions

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.

Also known as: recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
BMN 110 Weekly

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.

Placebo

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.

Also known as: recombinant human N-acetylgalactosamine-6-sulfatase, rhGALNS
BMN 110 Every Other Week

Eligibility Criteria

Age5 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

Unknown Facility

Oakland, California, United States

Location

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Wilmington, Delaware, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Córdoba, Argentina

Location

Unknown Facility

Campina Grande, Brazil

Location

Unknown Facility

Porto Alegre, Brazil

Location

Unknown Facility

Montreal, Canada

Location

Unknown Facility

Sherbrooke, Canada

Location

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Toronto, Canada

Location

Unknown Facility

Bogotá, Colombia

Location

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Copenhagen, Denmark

Location

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Lyon, France

Location

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Paris, France

Location

Unknown Facility

Mainz, Germany

Location

Unknown Facility

Monza, Italy

Location

Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Coimbra, Portugal

Location

Unknown Facility

Doha, Qatar

Location

Unknown Facility

Riyadh, Saudi Arabia

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

Taipei, Taiwan

Location

Unknown Facility

Birmingham, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Manchester, United Kingdom

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Mucopolysaccharidosis IVLysosomal Storage Diseases

Interventions

Chondroitinsulfatases

Condition Hierarchy (Ancestors)

MucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chondroitinases and Chondroitin LyasesSulfatasesEsterasesHydrolasesEnzymesEnzymes and Coenzymes

Results Point of Contact

Title
BioMarin Medical Information Services
Organization
BioMarin Pharmaceutical Inc.

Study Officials

  • Debra Lounsbury

    BioMarin Pharmaceutical

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2011

First Posted

January 12, 2011

Study Start

February 1, 2011

Primary Completion

August 1, 2012

Study Completion

August 1, 2012

Last Updated

July 7, 2014

Results First Posted

April 15, 2014

Record last verified: 2014-06

Locations