Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Study Overview

• Status: Terminated
• Conditions: Morquio A Syndrome; MPS IVA; Mucopolysaccharidosis IVA
• Intervention / Treatment: Drug: BMN 110

Detailed Description

Effect is defined by the following key domains:

• Upper extremity function and dexterity
• Mobility

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany
    • Universitätsklinikum Hamburg
  • Mainz, Germany
    • University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica
• United Kingdom
  • Birmingham, United Kingdom
    • NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital
  • Manchester, United Kingdom
    • Central Manchester University Hospitals NHS Foundation Trust
  • Salford, United Kingdom
    • Salford Royal NHS Foundation Trust
• United States
  • California
    • Oakland, California, United States
      • Children's Hospital & Research Center Oakland
  • Illinois
    • Chicago, Illinois, United States
      • Ann & Robert H. Lurie Children's Hospital of Chicago

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:

• Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
• Has 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.
• Is ≥ 5 years of age.
• If sexually active, is willing to use an acceptable method of contraception while participating in the study.
• Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
• Is willing and able to perform all study procedures as physically possible.

Exclusion Criteria:

• Is able to walk farther than a specified distance as assessed by the 6MWT.
• Has previous hematopoietic stem cell transplant (HSCT).
• Has received previous treatment with BMN 110.
• Has a known hypersensitivity to any of the components of BMN 110.
• Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study.
• Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments.
• Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
• Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 110 at 2.0 mg/kg/week; Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.	Drug: BMN 110; Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.; Other Names: ERT; N-acetylgalactosamine-6-sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; N-acetylgalactosamine-6-sulfate; sulfatase; elosulfase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)	FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).	Up to 96 weeks
Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT)	A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.	Up to 96 weeks
Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)	The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)	Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.	Up to 96 weeks

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Celeste Decker, M.D., BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 27, 2012
• First Posted (Estimate): October 2, 2012

Study Record Updates

• Last Update Posted (Estimate): January 12, 2016
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; Lysosomal Storage Disorder; GALNS; CPET; Mucopolysaccharidosis IVA; MPS IVA; Morquio A Syndrome; LSD; N-acetylgalactosamine-6-sulfatase; galactose-6-sulfatase; ERT; Mucopolysaccharidosis IVA Type A; MPS IVA Type A; N-acetylgalactosamine-6-sulfate; sulfatase; MOR-006; Limited ambulation; Grip/ Pinch
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis IV
• Other Study ID Numbers: MOR-006; 2011-005703-33 (EudraCT Number)