Clinical Trial: Study to Evaluate the Safety and Efficacy of Ace-ER Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Phase 3B Open-Label Extension Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy

Brief Summary: This open-label extension study of Ace-ER will assess the long-term safety and efficacy of Ace-ER treatment over a period of 24 months. Approximately 165 subjects from the UX001-CL202, UX001-CL301 and UX001-CL203 studies will be eligible to enroll in the study.

Detailed Summary: GNEM (or HIBM), is a severe, progressive myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Substrate replacement is a potential therapeutic strategy based on the success of replacing missing SA and reducing muscle disease in a relevant mouse model of the human disease. Successful use of SA replacement therapy in humans is believed to depend upon providing steady, long-term exposure to the compound in an extended-release form (such as Ace-ER), given SA's short half-life. This Phase 3b extension study will assess the long-term safety of Ace-ER in patients who participated in and completed the UX001-CL202, UX001-CL301, or UX001-CL203 studies; in addition, efficacy of 6 g/day Ace-ER will be further evaluated in GNEM patients, including those able to walk ≥200 m in the 6-minute walk test (6MWT) (roll over subjects from UX001-CL301 and naïve subjects from UX001-CL202) and GNEM patients with severe ambulatory impairment (roll over subjects from UX001-CL203).
Sponsor: Ultragenyx Pharmaceutical Inc

Current Primary Outcome: Evaluate the safety of ACE-ER [frequency of adverse events (AEs) and serious adverse events (SAEs)] [ Time Frame: Change from Baseline to Month (2,4 only for UX001-CL202 & UX001-CL301 subjects), 6, 12 18 and 24 ]

Original Primary Outcome: Evaluate the safety of ACE-ER [frequency of adverse events (AEs) and serious adverse events (SAEs)] [ Time Frame: Change from Baseline to Month (2,4 only for UX001-CL301 subjects), 6, 12 18 and 24 ]

Current Secondary Outcome:

  • Upper Extremity Composite Score by Dynamometry [ Time Frame: Change from Baseline to Month (2,4 only for UX001-CL202 & UX001-CL301 subjects), 6, 12 18 and 24 ]
  • Total Score on the GNE Myopathy Functional Activities Scale (GNEM-FAS) (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2, 4 , 6, 12, 18 and 24 ]
  • Total Score on the GNE Myopathy Functional Activities Scale (GNEM-FAS) - Expanded Version (UX001-CL203 subjects) [ Time Frame: Change from Baseline to Month 6, 12, 18 and 24 ]
  • Lower Extremity Composite Score (LEC) Score (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Lower Extremity Muscle Strength (UX001-CL202 & UX001-CL203 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Total Force (kg) versus Percent Predicted Force in the Knee Extensors (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
    Bilateral total force will be reported.
  • 6 Minute Walk Test Score (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
    The total distance walked (meters) in a six minute period will be measured.
  • Sit to Stand Test Score (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Number of Lifts in the 30-second Weighted Arm Lift Test (UX001-CL202 & UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]


Original Secondary Outcome:

  • Upper Extremity Composite Score by Dynamometry [ Time Frame: Change from Baseline to Month (2,4 only for UX001-CL301 subjects), 6, 12 18 and 24 ]
  • Total Score on the GNE Myopathy Functional Activities Scale (GNEM-FAS) (UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2, 4 , 6, 12, 18 and 24 ]
  • Total Score on the GNE Myopathy Functional Activities Scale (GNEM-FAS) - Expanded Version (UX001-CL203 subjects) [ Time Frame: Change from Baseline to Month 6, 12, 18 and 24 ]
  • Lower Extremity Composite Score (LEC) Score (UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Lower Extremity Muscle Strength (UX001-CL203 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Total Force (kg) versus Percent Predicted Force in the Knee Extensors (UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
    Bilateral total force will be reported.
  • 6 Minute Walk Test Score(UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
    The total distance walked (meters) in a six minute period will be measured.
  • Sit to Stand Test Score (UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]
  • Number of Lifts in the 30-second Weighted Arm Lift Test (UX001-CL301 subjects) [ Time Frame: Change from Baseline to Month 2,4, 6, 12, 18 and 24 ]


Information By: Ultragenyx Pharmaceutical Inc

Dates:
Date Received: April 4, 2016
Date Started: April 2016
Date Completion: May 18, 2020
Last Updated: May 9, 2017
Last Verified: May 2017