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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary: 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.
Sponsor: Ultragenyx Pharmaceutical Inc

Current Primary Outcome: 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.


Original Primary Outcome:

  • Efficacy of UX003 (US only) [ Time Frame: 24 weeks ]
    Efficacy determined by the proportion of subjects achieving a positive Individualized Clinical Response (ICR) outcome
  • Efficacy of UX003 (EU and rest of world) [ Time Frame: 24 weeks ]
    Efficacy determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline


Current Secondary Outcome:

  • 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.
  • 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.
  • Efficacy of UX003 by MDRI [ Time Frame: 24 weeks ]
    Measured by a multi-domain responder index (MDRI) following 24 weeks of UX003 exposure
  • Efficacy of UX003 by ICR [ Time Frame: 24 weeks ]
    Determined by the proportion of subjects achieving a positive individualized clinical response (ICR) outcome.
  • 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.


Original Secondary Outcome:

  • 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.
  • Clinical Effects [ Time Frame: 48 weeks ]
    Clinical effects including pulmonary function, walking distance, shoulder flexion, fine motor function and gross motor function
  • Efficacy of UX003 (US only) [ Time Frame: 24 weeks ]
    Efficacy determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline


Information By: Ultragenyx Pharmaceutical Inc

Dates:
Date Received: August 22, 2014
Date Started: November 2014
Date Completion:
Last Updated: May 12, 2017
Last Verified: May 2017