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

NCT ID: NCT01275066

Last Updated: 2014-07-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

177 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2012-08-31

Brief Summary

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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

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Conditions

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MPS IV A

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

BMN 110 Weekly

Group Type EXPERIMENTAL

BMN 110 Weekly

Intervention Type DRUG

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.

BMN 110 Every Other Week

Group Type EXPERIMENTAL

BMN 110 Every Other Week

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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recombinant human N-acetylgalactosamine-6-sulfatase rhGALNS recombinant human N-acetylgalactosamine-6-sulfatase rhGALNS

Eligibility Criteria

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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.
Minimum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BioMarin Pharmaceutical

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Debra Lounsbury

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

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Oakland, California, United States

Site Status

Wilmington, Delaware, United States

Site Status

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

Site Status

Chicago, Illinois, United States

Site Status

New York, New York, United States

Site Status

Seattle, Washington, United States

Site Status

Córdoba, , Argentina

Site Status

Campina Grande, , Brazil

Site Status

Porto Alegre, , Brazil

Site Status

Montreal, , Canada

Site Status

Sherbrooke, , Canada

Site Status

Toronto, , Canada

Site Status

Bogotá, , Colombia

Site Status

Copenhagen, , Denmark

Site Status

Lyon, , France

Site Status

Paris, , France

Site Status

Mainz, , Germany

Site Status

Monza, , Italy

Site Status

Tokyo, , Japan

Site Status

Amsterdam, , Netherlands

Site Status

Coimbra, , Portugal

Site Status

Doha, , Qatar

Site Status

Riyadh, , Saudi Arabia

Site Status

Seoul, , South Korea

Site Status

Taipei, , Taiwan

Site Status

Birmingham, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Countries

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United States Argentina Brazil Canada Colombia Denmark France Germany Italy Japan Netherlands Portugal Qatar Saudi Arabia South Korea Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 25487082 (View on PubMed)

Related Links

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http://www.bmrn.com

BioMarin Pharmaceutical Inc. website

Other Identifiers

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2010-020198-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

10/H1306/87

Identifier Type: OTHER

Identifier Source: secondary_id

18972/0213/001-0001

Identifier Type: OTHER

Identifier Source: secondary_id

2011_038#B201129

Identifier Type: OTHER

Identifier Source: secondary_id

145240

Identifier Type: OTHER

Identifier Source: secondary_id

2011-01-09

Identifier Type: OTHER

Identifier Source: secondary_id

20110012889

Identifier Type: OTHER

Identifier Source: secondary_id

0999935174

Identifier Type: OTHER

Identifier Source: secondary_id

MOR-004

Identifier Type: -

Identifier Source: org_study_id

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