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

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)

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).

Study Overview

• Status: Completed
• Conditions: MPS IV A
• Intervention / Treatment: Drug: BMN 110

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
  • London, United Kingdom
  • Manchester, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BMN 110; Within-patient Dose-Escalation

Drug: BMN 110; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Celeste Decker, MD, BioMarin Pharmceutical Inc.

Publications and helpful links

General Publications

• Hendriksz C, Santra S, Jones SA, Geberhiwot T, Jesaitis L, Long B, Qi Y, Hawley SM, Decker C. Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002/MOR-100), representing 5 years of treatment. Mol Genet Metab. 2018 Apr;123(4):479-487. doi: 10.1016/j.ymgme.2018.02.011. Epub 2018 Feb 19.

Helpful Links

• BioMarin Pharmaceutical Inc. website
• The BioMarin Morquio Program

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: April 10, 2009
• First Submitted That Met QC Criteria: April 17, 2009
• First Posted (Estimate): April 21, 2009

Study Record Updates

• Last Update Posted (Estimate): June 30, 2014
• Last Update Submitted That Met QC Criteria: May 28, 2014
• Last Verified: May 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-002