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A Phase 3 Study of UX003 rhGUS Enzyme Replacement Therapy in Patients With MPS 7

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ClinicalTrials.gov Identifier: NCT02230566
Recruitment Status : Completed
First Posted : September 3, 2014
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The Phase 3 study will use a novel randomized, intra-subject placebo-controlled, single crossover design, referred to as Blind Start, to evaluate the safety and efficacy of UX003.

Condition or disease Intervention/treatment Phase
MPS 7 Sly Syndrome Mucopolysaccharidosis MPS VII Drug: UX003 Other: Placebo Phase 3

Detailed Description:
The Blind Start is a novel design whereby subjects will be randomized to one of 4 groups, each representing a different treatment sequence, and cross over to UX003 at different pre-defined time points in a blinded manner. All groups will receive a minimum of 24 weeks treatment with 4 mg/kg UX003 every other week.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-Controlled, Blind-Start, Single-Crossover Phase 3 Study to Assess the Efficacy and Safety of UX003 rhGUS Enzyme Replacement Therapy in Patients With MPS 7
Study Start Date : November 2014
Primary Completion Date : May 2016
Study Completion Date : May 2016


Arms and Interventions

Arm Intervention/treatment
Experimental: A: 4mg/kg of UX003
Group A will receive 4 mg/kg UX003 every other week
Drug: UX003
UX003 is a sterile liquid buffered saline formulation of rhGUS
Other Names:
  • recombinant human beta-glucuronidase
  • rh-β-glucuronidase
  • rhGUS
Experimental: B: 8wks Placebo then 4mg/kg UX003
Group B will receive placebo every other week for the first 8 weeks followed by 4 mg/kg UX003 every other week
Drug: UX003
UX003 is a sterile liquid buffered saline formulation of rhGUS
Other Names:
  • recombinant human beta-glucuronidase
  • rh-β-glucuronidase
  • rhGUS
Other: Placebo
Placebo consisting of the UX003 formulation buffer (without rhGUS)
Other Name: Reference therapy
Experimental: C: 16wks Placebo then 4mg/kg UX003
Group C will receive placebo every other week for the first 16 weeks followed by 4 mg/kg UX003 every other week
Drug: UX003
UX003 is a sterile liquid buffered saline formulation of rhGUS
Other Names:
  • recombinant human beta-glucuronidase
  • rh-β-glucuronidase
  • rhGUS
Other: Placebo
Placebo consisting of the UX003 formulation buffer (without rhGUS)
Other Name: Reference therapy
Experimental: D: 24wks Placebo then 4mg/kg UX003
Group D will receive placebo every other week for the first 24 weeks followed by 4 mg/kg UX003 every other week
Drug: UX003
UX003 is a sterile liquid buffered saline formulation of rhGUS
Other Names:
  • recombinant human beta-glucuronidase
  • rh-β-glucuronidase
  • rhGUS
Other: Placebo
Placebo consisting of the UX003 formulation buffer (without rhGUS)
Other Name: Reference therapy


Outcome Measures

Primary Outcome Measures :
  1. Efficacy of UX003 (US only) [ Time Frame: 48 weeks ]
    Efficacy determined by the totality of the clinical data on a per subject basis. No primary endpoint will be declared.


Secondary Outcome Measures :
  1. Efficacy of UX003 (primary endpoint in EU and rest of world & secondary objective in US) [ Time Frame: 24 weeks ]
    Efficacy determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline.

  2. Safety and Tolerability of UX003 [ Time Frame: 48 weeks ]
    Safety and tolerability following up to 48 weeks of UX003 exposure. Safety evaluations will include standard adverse events and laboratory assessments as well as Adverse Physiology Related Group (APRG) safety reporting, a novel method synthesizing safety symptoms in multi-domain physiology related groups to capture infusion-associated reaction (IAR) information.

  3. Efficacy of UX003 by MDRI [ Time Frame: 24 weeks ]
    Measured by a multi-domain responder index (MDRI) following 24 weeks of UX003 exposure

  4. Efficacy of UX003 by ICR [ Time Frame: 24 weeks ]
    Determined by the proportion of subjects achieving a positive individualized clinical response (ICR) outcome.

  5. Efficacy and Tolerability of UX003 [ Time Frame: 24 weeks ]
    Clinical effects including pulmonary function, walking distance, shoulder flexion, fine motor function and gross motor function.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing
  • Elevated uGAG excretion at a minimum of 3-fold over the mean normal for age (at Screening)
  • 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
  • Aged 5 - 35 years, inclusive
  • Willing and able to provide written 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.
  • 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 Screening 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 Screening, or who have had total hysterectomy.
  • Naïve to treatment with UX003

Exclusion Criteria:

  • Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells
  • Major surgery within 3 months prior to study entry or planned major surgery during the study that may not allow safe participation in the study
  • 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 Screening or planning to become pregnant (self or partner) at any time during the study
  • Use of any investigational product (drug or device or combination) within 30 days prior to Screening, 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 participation in the study.
  • 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.
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT02230566


Locations
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, Florida
Miami Children's Hospital
Miami, Florida, United States, 33155
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
Principal Investigator: Paul Harmatz, MD Children's Hospital & Research Center Oakland
Principal Investigator: Raymond Wang, MD Children’s Hospital of Orange County
Principal Investigator: Mislen Bauer, MD Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Principal Investigator: Chester Whitley, MD University of Minnesota - Clinical and Translational Science Institute
More Information

Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02230566     History of Changes
Other Study ID Numbers: UX003-CL301
First Posted: September 3, 2014    Key Record Dates
Last Update Posted: May 15, 2017
Last Verified: May 2017

Keywords provided by Ultragenyx Pharmaceutical Inc:
MPS 7
Sly Syndrome
Mucopolysaccharidosis
MPS VII
Enzyme Replacement Therapy
Mucopolysaccharidosis type 7
rare disease
lysosomal storage disease
metabolic disorder

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