Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

• ClinicalTrials.gov Identifier: NCT01697319
• Recruitment Status: Terminated
• First Posted: October 2, 2012
• Results First Posted: January 12, 2016
• Last Update Posted: January 12, 2016
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Study Description

Brief Summary:

The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

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

Detailed Description:

Effect is defined by the following key domains:

• Upper extremity function and dexterity
• Mobility

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation
• Study Start Date: August 2012
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: BMN 110 at 2.0 mg/kg/week; Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 144 weeks.	Drug: BMN 110; Drug will be delivered through a 4 hour (approximate) IV infusion at a dosage amount of 2.0 mg/kg/week for up to 144 weeks of treatment.; Other Names: N-acetylgalactosamine-6-sulfatase; N-acetylgalactosamine-6-sulfate; sulfatase; galactose-6-sulfatase; GALNS; enzyme replacement therapy; ERT; elosulfase alfa

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) [ Time Frame: Up to 96 weeks ]
   FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
2. Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) [ Time Frame: Up to 96 weeks ]
   A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
3. Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) [ Time Frame: Up to 96 weeks ]
   The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.

Secondary Outcome Measures :

1. Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) [ Time Frame: Up to 96 weeks ]
   Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Is willing and able to provide written, signed informed consent (or their legally authorized representative) after the nature of the study has been explained and prior to performance of any research-related procedure. Patients who do not meet country and local age requirements for informed consent must be willing and able to provide written assent after the nature of the study has been explained and prior to performance of any research-related procedure.
• Has documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
• Is ≥ 5 years of age.
• If sexually active, is willing to use an acceptable method of contraception while participating in the study.
• Females of childbearing potential must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests during the study.
• Is willing and able to perform all study procedures as physically possible.

Exclusion Criteria:

• Is able to walk farther than a specified distance as assessed by the 6MWT.
• Has previous hematopoietic stem cell transplant (HSCT).
• Has received previous treatment with BMN 110.
• Has a known hypersensitivity to any of the components of BMN 110.
• Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the first 24 weeks of the study.
• Has used any other investigational product or investigational medical device within 30 days prior to the Screening Visit or requires any investigational agent prior to completion of all scheduled study assessments.
• Is pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study.
• Has a concurrent disease or condition, including but not limited to symptomatic cervical spine instability or severe cardiac disease or complete paralysis due to a spinal cord injury (defined as an inability to move arms and legs), that would interfere with study participation or safety as determined by the Investigator.
• Has 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.

Contacts and Locations

Locations

United States, California

Children's Hospital & Research Center Oakland

Oakland, California, United States

United States, Illinois

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Germany

Universitätsklinikum Hamburg

Hamburg, Germany

University Medical Center Mainz, Center of Pediatric and Adolescent Medicine Villa Metabolica

Mainz, Germany

United Kingdom

NIHR/Wellcome Trust Birmingham CRF, Queen Elizabeth Hospital

Birmingham, United Kingdom

Central Manchester University Hospitals NHS Foundation Trust

Manchester, United Kingdom

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

• Study Director: Celeste Decker, M.D.; BioMarin Pharmaceutical

More Information

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT01697319
• Other Study ID Numbers: MOR-006; 2011-005703-33 ( EudraCT Number )
• First Posted: October 2, 2012
• Results First Posted: January 12, 2016
• Last Update Posted: January 12, 2016
• Last Verified: December 2015

Keywords provided by BioMarin Pharmaceutical:

Morquio A Syndrome; Mucopolysaccharidosis IVA Type A; MPS IVA 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; MOR-006; CPET; Limited ambulation; Grip/ Pinch

Additional relevant MeSH terms:

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