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

Phase 1

Completed

Brief Summary: 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).

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
BMN 110	BMN 110	Within-patient Dose-Escalation

Primary Outcome Measures

Name	Time	Method
Subject Incidence of Treatment Emergent AEs	Entire Study, through week 84	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in 6MWT	Baseline to Weeks 12, 24, 36, 48, 72	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.
Change From Baseline in 3MSCT	Baseline to Weeks 12, 24, 36, 48, 72	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.
Percent Change From Baseline in uKS	Baseline to Weeks 12, 24, 36, 72	Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value \*100%
Percent Change From Baseline in MVV	Baseline to Weeks 12, 24, 36, 72	Percent Change from baseline in Maximum Voluntary Ventilation.
Percent Change From Baseline in FVC	Baseline to Weeks 12, 24, 36, 72	Percent Change from baseline in Forced Vital Capacity.