A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA

Study Overview
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Brief Summary
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This multicenter, open-label study is designed to assess safety, dose-response using pharmacokinetic (PK) and pharmacodynamic (PD) measures, and clinical efficacy of BMN 110 in subjects between 5 and 18 years of age, diagnosed with Mucopolysaccharidosis IVA (MPS IVA).

Official Title
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A Phase 1/2, Multicenter, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)

Conditions
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MPS IV A

Intervention / Treatment
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* Drug: BMN 110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA. Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, 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. Between 5 and 18 years of age, inclusive. Sexually active subjects 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. Willing to perform all study procedures as physically possible. Exclusion Criteria: Previous hematopoietic stem cell transplant (HSCT). Has known hypersensitivity to BMN 110 or its excipients. 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 that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability. Any condition that, in the view of the Principal Investigator (PI), places the subject 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
Maximum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMN 110<br>Within-patient Dose-Escalation | Drug: BMN 110<br>* Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Incidence of Treatment Emergent AEs | The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA. The safety variable incidence of TEAE is summarized. | Entire Study, through week 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 6MWT | Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes. | Baseline to Weeks 12, 24, 36, 48, 72 | 
| Change From Baseline in 3MSCT | Change from baseline in the 3-minute Stair Climb Test. Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute. | Baseline to Weeks 12, 24, 36, 48, 72 | 
| Percent Change From Baseline in uKS | Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100% | Baseline to Weeks 12, 24, 36, 72 | 
| Percent Change From Baseline in MVV | Percent Change from baseline in Maximum Voluntary Ventilation. | Baseline to Weeks 12, 24, 36, 72 | 
| Percent Change From Baseline in FVC | Percent Change from baseline in Forced Vital Capacity. | Baseline to Weeks 12, 24, 36, 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS IVA, Mucopolysaccharidosis IV type A, MPS IV Type A, Mucopolysaccharidosis IVA, Morquio A Syndrome, Lysosomal Storage Disorder, LSD, N-acetylgalactosamine-6-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, galactose-6-sulfatase, GALNS, enzyme replacement therapy, ERT