A Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Study Description

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Brief Summary:

This multicenter, open-label extension study is designed to assess long-term efficacy and safety of 2.0 milligrams (mg)/kilogram(kg)/week of BMN 110 in patients diagnosed with Mucopolysaccharidosis IVA (MPS IVA). Patients with MPS IVA, who enrolled in a prior BioMarin sponsored clinical study of BMN 110 (NCT00884949; Study Identification Number MOR-002), were eligible to enroll in this study (except patients who enrolled in NCT01275066; Study Identification Number MOR-004).

Condition or disease	Intervention/treatment	Phase
MPS IV A; Mucopolysaccharidosis IVA; Morquio A Syndrome	Drug: BMN 110	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Multinational, Open-Label, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Study Start Date :	November 2010
Actual Primary Completion Date :	July 2014
Actual Study Completion Date :	July 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: BMN 110	Drug: BMN 110; Patients will receive an intravenous infusion of BMN110 at 2.0mg/kg/week, over a period of approximately 4 hours per infusion, for up to 240 weeks.

Outcome Measures

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Primary Outcome Measures :

1. Safety Evaluation [ Time Frame: Entire Study Period, up to 240 weeks ]

   The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs).

   The primary outcome measure data is presented in more detail under the Adverse Events section.

Secondary Outcome Measures :

1. Change From Baseline in Endurance as Measured by the 6-minute Walk Test During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [ Time Frame: Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial ]
   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.
2. Change in Baseline in Endurance as Measured by the 3 Minute Stair Climb During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [ Time Frame: Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial ]
   Change from baseline in the 3-minute Stair Climb Test (3MSCT). 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.
3. Percent Change From Baseline in Urine Keratan Sulfate (uKS) Levels During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [ Time Frame: Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 168 weeks during the MOR-100 extension trial ]
   Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%
4. Percent Change From Baseline in Respiratory Function Test MVV During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [ Time Frame: Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial ]
   Percent Change from baseline in Maximum Voluntary Ventilation.
5. Percent Change From Baseline in Respiratory Function Test FVC During the Pilot Trial (MOR-002) and Current Extension Trial (MOR-100). [ Time Frame: Baseline and every 12 weeks for up to 72 weeks during the MOR-002 pilot trial and every 24 weeks for up to 192 weeks during the MOR-100 extension trial ]
   Percent Change from baseline in Forced Vital Capacity.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), 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.
• Sexually active patients 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 Baseline and be willing to have additional pregnancy tests during the study.
• Must have enrolled in a prior BioMarin sponsored clinical study of BMN 110.

Exclusion Criteria:

• Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product (other than BMN 110 in a prior clinical study) or investigational medical device within 30 days prior to Baseline, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Concurrent disease or condition, including but not limited to symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation or safety as determined by the Investigator.
• 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.
• Were enrolled in MOR-004 (patients from MOR-004 may be eligible to participate in a separate, appropriately designed, extension study).

Contacts and Locations

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Locations

United Kingdom
Birmingham, United Kingdom
Dumfries, United Kingdom
London, United Kingdom
Manchester, United Kingdom

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

Study Director:	Celeste Decker, MD	BioMarin Pharmaceutical

More Information

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Additional Information:

BioMarin Pharmaceutical Inc. website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:	NCT01242111 History of Changes
Other Study ID Numbers:	MOR-100
First Posted:	November 16, 2010
Results First Posted:	September 30, 2015
Last Update Posted:	September 30, 2015
Last Verified:	August 2015

Keywords provided by BioMarin Pharmaceutical:

Morquio A Syndrome; Mucopolysaccharidosis IV type A; MPS IV Type A; Mucopolysaccharidosis IVA; MPS IVA; Lysosomal Storage Disorder; LSD	N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT

Additional relevant MeSH terms:

Syndrome; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Disease; Pathologic Processes; Carbohydrate Metabolism, Inborn Errors	Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases