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

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)

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.

Study Overview

• Status: Completed
• Conditions: MPS IV A
• Intervention / Treatment: Drug: Placebo; Drug: BMN 110 Weekly; Drug: BMN 110 Every Other Week

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina
• Brazil
  • Campina Grande, Brazil
  • Porto Alegre, Brazil
• Canada
  • Montreal, Canada
  • Sherbrooke, Canada
  • Toronto, Canada
• Colombia
  • Bogota, Colombia
• Denmark
  • Copenhagen, Denmark
• France
  • Lyon, France
  • Paris, France
• Germany
  • Mainz, Germany
• Italy
  • Monza, Italy
• Japan
  • Tokyo, Japan
• Korea, Republic of
  • Seoul, Korea, Republic of
• Netherlands
  • Amsterdam, Netherlands
• Portugal
  • Coimbra, Portugal
• Qatar
  • Doha, Qatar
• Saudi Arabia
  • Riyadh, Saudi Arabia
• Taiwan
  • Taipei, Taiwan
• United Kingdom
  • Birmingham, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom
• United States
  • California
    • Oakland, California, United States
  • Delaware
    • Wilmington, Delaware, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Illinois
    • Chicago, Illinois, United States
  • New York
    • New York, New York, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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.
Experimental: BMN 110 Weekly	Drug: 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.; Other Names: recombinant human N-acetylgalactosamine-6-sulfatase; rhGALNS
Experimental: BMN 110 Every Other Week	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.; Other Names: recombinant human N-acetylgalactosamine-6-sulfatase; rhGALNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Endurance as Measured by the 6-minute Walk Test	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Publications and helpful links

General Publications

• 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.

Helpful Links

• BioMarin Pharmaceutical Inc. website

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: January 11, 2011
• First Posted (Estimate): January 12, 2011

Study Record Updates

• Last Update Posted (Estimate): July 7, 2014
• Last Update Submitted That Met QC Criteria: June 6, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; Lysosomal Storage Disorder; GALNS; Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; LSD; N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; ERT
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses
• Other Study ID Numbers: MOR-004; 2010-020198-18 (EudraCT Number); 10/H1306/87 (Other Identifier: National Research Ethics Service); 18972/0213/001-0001 (Other Identifier: Medicines and Healthcare Products Regulatory Agency); 2011_038#B201129 (Other Identifier: Medical Ethics Review Committee (METC)); 145240 (Other Identifier: Health Canada); 2011-01-09 (Other Identifier: Committee for the Protection of Personnes); 20110012889 (Other Identifier: Korean Food & Drug Administration (KFDA)); 0999935174 (Other Identifier: Taiwan FDA)