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

MPS IV A Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00884949
• Other study ID #: MOR-002
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 10, 2009
• Last updated: May 28, 2014
• Start date: April 2009
• Est. completion date: March 2011

Study information

• Verified date: May 2014
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 18 Years

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• MPS IV A
• Mucopolysaccharidoses

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Percent Change From Baseline in MVV	Percent Change from baseline in Maximum Voluntary Ventilation.	Baseline to Weeks 12, 24, 36, 72	No
Secondary	Percent Change From Baseline in FVC	Percent Change from baseline in Forced Vital Capacity.	Baseline to Weeks 12, 24, 36, 72	No

External Links

•   BioMarin Pharmaceutical Inc. website