A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
Condition: MPS 7; Sly Syndrome; Mucopolysaccharidosis; MPS VII
MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis VII
Intervention: UX003; Placebo
Intervention description: UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion; Placebo consisting of the UX003 formulation buffer (without rhGUS)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 5 Years
Maximum age: 35 Years
Healthy volunteers: No
Keywords: MPS 7; Sly Syndrome; Mucopolysaccharidosis; MPS VII; Enzyme Replacement Therapy; Mucopolysaccharidosis type 7; rare disease; lysosomal storage disease; metabolic disorder

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.
      The Blind Start is a novel design whereby participants will be randomized to 1 of 4 groups,
      each representing a different treatment sequence, and will 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 (QOW).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme
             assay or genetic testing.

          -  Elevated urinary glycosaminoglycan (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.