Clinical Trial: A Phase 2 Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy

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

Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myop

Brief Summary: GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA).

Detailed Summary: GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Substrate replacement therapy 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 (Malicdan et al., 2009). 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 Sialic Acid-Extended Release [SA-ER]), given SA's short half-life. Following a Phase 1 study to establish the pharmacokinetics (PK) for SA-ER, Ultragenyx is conducting this study to assess the dose and potential pharmacodynamic effect of restoring sialylation of muscle by treatment with SA-ER at two dose levels as compared to placebo when administered over two 24 week periods of time. The study will also evaluate safety, as well as the effect of SA-ER on clinical measures of muscle strength, mobility, function and self-reported disability and quality of life. Effects on muscle volume/mass and function and on serum biomarkers will be evaluated as exploratory measures. These data should allow the selection of a dose and the appropriate design for a Phase 3 clinical study.
Sponsor: Ultragenyx Pharmaceutical Inc

Current Primary Outcome: Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM. [ Time Frame: Baseline, Week 24, and Week 48 ]

To evaluate the effect of SA-ER treatment on improvement of biochemical measures of sialylation and pathology in muscle. On mobility, strength, and function using a series of quantitative and physical performance measures and quality of life using patient-reported outcome measures.


Original Primary Outcome: Change from baseline in total SA bound to muscle proteins and lipids and free SA will be determined on muscle biopsies taken at 24 and 48 weeks. [ Time Frame: The same muscles will be evaluated by biopsy at Baseline, 24, and 48 weeks for each subject. ]

The choice of muscle will depend on the MRI evaluation at Screening, and the same muscles will be evaluated at Baseline, 24, and 48 weeks for each subject. Sialylation of polysialylated neural cell adhesion molecule (PSA-NCAM) will also be determined in these biopsies.


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Ultragenyx Pharmaceutical Inc

Dates:
Date Received: January 17, 2012
Date Started: May 2012
Date Completion:
Last Updated: June 14, 2016
Last Verified: June 2016