An Open-Label Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Treatment in Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7) Patients Less Than 5 Years of Age

• Sponsor: Ultragenyx Pharmaceutical Inc
• Information provided by (Responsible Party): Ultragenyx Pharmaceutical Inc

Study Description

Brief Summary:

UX003-CL203 is an open-label, multi-center, Phase 2 study to assess the safety and efficacy of UX003 in pediatric MPS 7 subjects.

Condition or disease	Intervention/treatment	Phase
Sly Syndrome; MPS VII; Mucopolysaccharidosis; Mucopolysaccharidosis VII	Drug: UX003	Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-label Study of UX003 rhGUS Enzyme Replacement Therapy in MPS 7 Patients Less Than 5 Years Old
Actual Study Start Date :	July 21, 2015
Actual Primary Completion Date :	March 26, 2019
Actual Study Completion Date :	March 26, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 4 mg/kg of UX003; Initial treatment period 48 weeks. Continuation period up to 240 weeks.	Drug: UX003; Other Names: recombinant human beta-glucoronidase; rhGUS; Mepsevii ™; vestronidase alfa-vjbk; vestronidase alfa

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Urinary Glycosaminoglycans (uGAG) Excretion at Week 48 [ Time Frame: Baseline (Week 0), Week 48 ]
   Determined by the percent reduction of uGAG excretion after 48 weeks of treatment relative to the pre-treatment baseline.
2. Safety and tolerability of UX003 (severity, frequency, and number of Adverse Events and Serious Adverse Events) [ Time Frame: Initial treatment period 48 weeks. Continuation period up to 240 weeks. ]

Secondary Outcome Measures :

1. Change From Baseline in Growth Velocity at Week 48 [ Time Frame: Baseline (Week 0), Week 48 ]
   Determined by changes in growth velocity after 48 weeks of treatment relative to pre-treatment baseline and published normative data for age and gender.
2. Change From Baseline in Hepatosplenomegaly at Week 48 [ Time Frame: Baseline (Week 0), Week 48 ]
   Determined by the volume of the liver and spleen after 48 weeks of treatment relative to pre-treatment baseline and normal values for age and gender.

Eligibility Criteria

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Ages Eligible for Study:	up to 5 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay, or genetic testing.
2. Under 5 years of age at the time of informed consent.
3. Written informed consent of Legally Authorized Representative after the nature of the study has been explained, and prior to any research-related procedures.

Exclusion Criteria:

1. Undergone a successful bone marrow or stem cell transplant or has evidence of any degree of detectable chimaerism with donor cells.
2. Any known hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
3. Use of any investigational product (drug or device or combination) other than UX003 within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments at any time during the study.
4. Has a condition of such severity and acuity, in the opinion of the Investigator, which may not allow safe study participation. For patients with hydrops fetalis, the ongoing interventions to manage fluid balance can be continued; if the addition of enzyme replacement therapy (ERT) is considered a fluid-overload risk, the individual should be excluded.
5. Has a concurrent disease or condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or affect safety. Since hydropic patients have a high rate of mortality, the risk of death prior to 1 year of age should not be considered sufficient to exclude the patient from the study for compliance.

Contacts and Locations

Locations

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United States, District of Columbia
Children's National Health System
Washington, District of Columbia, United States, 20010
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10038
United States, Utah
University of Utah Hospital
Salt Lake City, Utah, United States, 84132
Portugal
Centro Hospitalar do Porto
Porto, Portugal, 4099-345
Spain
Hospital Universitario Virgen Del Rocio
Sevilla, Spain, 41013

Sponsors and Collaborators

Ultragenyx Pharmaceutical Inc

Investigators

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Study Director:	Medical Director	Ultragenyx Pharmaceutical Inc

More Information

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

Qi Y, McKeever K, Taylor J, Haller C, Song W, Jones SA, Shi J. Pharmacokinetic and Pharmacodynamic Modeling to Optimize the Dose of Vestronidase Alfa, an Enzyme Replacement Therapy for Treatment of Patients with Mucopolysaccharidosis Type VII: Results from Three Trials. Clin Pharmacokinet. 2019 May;58(5):673-683. doi: 10.1007/s40262-018-0721-y. Erratum in: Clin Pharmacokinet. 2018 Dec 4;:.

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Responsible Party:	Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier:	NCT02418455 History of Changes
Other Study ID Numbers:	UX003-CL203; 2015-000104-26 ( EudraCT Number )
First Posted:	April 16, 2015
Last Update Posted:	April 2, 2019
Last Verified:	April 2019

Keywords provided by Ultragenyx Pharmaceutical Inc:

MPS 7; Sly Syndrome; MPS VII; Enzyme Replacement Therapy	Rare Disease; Mucopolysaccharidosis type 7; Lysosomal Storage Disease; Metabolic Disorder

Additional relevant MeSH terms:

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