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

Study Overview
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Brief Summary
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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.

Detailed Description
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Effect is defined by the following key domains: Upper extremity function and dexterity Mobility

Official Title
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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

Conditions
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Mucopolysaccharidosis IVA, Morquio A Syndrome, MPS IVA

Intervention / Treatment
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* Drug: BMN 110


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMN 110 at 2.0 mg/kg/week<br>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<br>* 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.<br>* Other names: elosulfase alfa;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LSD, Lysosomal Storage Disorder, N-acetylgalactosamine-6-sulfate, Mucopolysaccharidosis IVA Type A, MPS IVA Type A, Mucopolysaccharidosis IVA, MPS IVA, Morquio A Syndrome, N-acetylgalactosamine-6-sulfatase, sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT, MOR-006, CPET, Limited ambulation, Grip/ Pinch