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A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02432144
Recruitment Status : Completed
First Posted : May 1, 2015
Last Update Posted : January 18, 2019
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:
UX003-CL202 is an open-label, multi-center extension study to assess long-term safety and efficacy of UX003 treatment in patients with MPS 7.

Condition or disease Intervention/treatment Phase
Sly Syndrome MPS VII Mucopolysaccharidosis Mucopolysaccharidosis VII Drug: UX003 Phase 3

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

Detailed Description:

Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome) is an ultra-rare (< 100 cases currently identified worldwide), chronically debilitating and life threatening lysosomal storage disease. It is characterized by a deficiency of the lysosomal enzyme beta-glucuronidase (GUS), required for degradation of the glycosaminoglycans (GAGs): dermatan sulfate (DS), chondroitin-6-sulfate (CS) and heparan sulfate (HS). The GUS deficiency results in lysosomal accumulation of GAGs in multiple tissues and organs throughout the body and numerous clinical signs and symptoms as a result of tissue damage and organ dysfunction. There are currently no approved treatments for MPS 7.

UX003 (recombinant human beta glucuronidase, rhGUS) is intended as a long-term enzyme replacement therapy (ERT) for the treatment of MPS 7 via intravenous (IV) administration. Ultragenyx is conducting this treatment and extension study to assess the long-term safety and efficacy of UX003 treatment in subjects with MPS 7. Subjects with MPS 7 who are UX003 treatment-naïve or have been previously enrolled and treated with UX003 in other clinical studies or programs are eligible for enrollment.

The study will continue for up to 144 weeks or until one of the following occurs: the subject withdraws consent and discontinues from the study, the subject is discontinued from the study at the discretion of the Investigator or Ultragenyx, or the study is terminated.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7
Actual Study Start Date : November 10, 2015
Actual Primary Completion Date : January 14, 2019
Actual Study Completion Date : January 14, 2019

Arm Intervention/treatment
Experimental: 4 mg/kg of UX003
All subjects will receive 4 mg/kg UX003 every other week (QOW) unless data from prior studies define a different dose either for that subject or the use of UX003 in general.
Drug: UX003
UX003 is a sterile liquid buffered saline formulation of rhGUS that contains enzyme at a concentration of 2 mg/mL filled to allow the withdrawal of a 5.0 mL deliverable volume and supplied in a 10 mL glass vial. UX003 will be administered QOW by slow intravenous (IV) infusion over approximately 4 hours. Infusions will be administered on a rate schedule involving a slower infusion rate initially followed by an increase in rate to minimize the potential for infusion-associated reactions (IARs); the infusion rate may be slowed to manage or reduce IARs.
Other Names:
  • recombinant human beta-glucoronidase
  • rhGUS
  • Mepsevii ™
  • vestronidase alfa
  • vestronidase alfa-vjbk

Primary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs), Treatment-Related AEs, and Serious Adverse Events (SAEs) [ Time Frame: 144 weeks ]

Secondary Outcome Measures :
  1. Percent Reduction From Baseline at Week 144 in uGAG Excretion [ Time Frame: 144 weeks ]
    First morning void urine will be evaluated for uGAG concentration and normalized to urinary creatinine concentration.

  2. Change From Baseline at Week 144 in uGAG Excretion [ Time Frame: 144 weeks ]
    First morning void urine will be evaluated for uGAG concentration and normalized to urinary creatinine concentration.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing.
  • Willing and able to provide written, signed informed consent or, in the case of subjects 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.
  • Willing and able to comply with all study procedures.
  • Sexually active subjects must be willing to use acceptable, highly-effective methods of contraception while participating in the study and for 30 days following the last dose.
  • Females of childbearing potential must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, or have had tubal ligation at least one year prior to completion of the primary study, or have had total hysterectomy.
  • For UX003 treatment-naïve subjects only, apparent clinical signs of lysosomal storage disease as judged by the Investigator, including at least one of the following: enlarged liver and spleen, joint limitations, airway obstruction or pulmonary problems, limitation of mobility while still ambulatory.
  • For UX003 treatment-naïve subjects only, elevated uGAG excretion at a minimum of 2-fold over normal.
  • For UX003 treatment-naïve subjects only, aged 5 years and older.

Exclusion Criteria:

  • If enrolled in a prior UX003 clinical study, the subject experienced safety-related event(s) in the prior UX003 clinical study that, in the opinion of the Investigator and sponsor, precludes resuming UX003 treatment.
  • Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.
  • Presence or history of any hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
  • Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study.
  • Other than the use of UX003, use of any investigational product (drug or device or combination) within 30 days prior to Baseline, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  • Presence of a condition of such severity and acuity that, in the opinion of the Investigator, warrants immediate surgical intervention or other treatment or may not allow safe study participation.
  • Concurrent disease or condition, or laboratory abnormality 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 introduce additional safety concerns.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02432144

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United States, California
Children's Hospital Oakland
Oakland, California, United States, 94609
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Hospital Infantil Candido Fontoura Sao Paulo
Sao Paulo, Brazil
Centenario Hospital Miguel Hidalgo, Pediatrics
Aguascalientes, Mexico, 20230
Unidade de Doenças Metabólicas - Centro Hospitalar do Porto
Porto, Portugal, 4099-001
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
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Study Director: Medical Director Ultragenyx Pharmaceuticals, Inc.

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Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT02432144     History of Changes
Other Study ID Numbers: UX003-CL202
2015-001875-32 ( EudraCT Number )
First Posted: May 1, 2015    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019

Keywords provided by Ultragenyx Pharmaceutical Inc:
Sly Syndrome
Enzyme Replacement Therapy
Rare Disease
Mucopolysaccharidosis Type 7
Lysosomal Storage Disease
Metabolic Disorder

Additional relevant MeSH terms:
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Mucopolysaccharidosis VII
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases