A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of ManNAc in Subjects with GNE Myopathy

GNE myopathy is a slowly progressive muscle disease resulting in marked disability, including wheelchair use, and ultimately requiring dependent care and for which there is no treatment available. This trial will evaluate the efficacy of N-acetyl-D-mannosamine monohydrate (ManNAc) in a randomized-placebo- controlled, double-blind study of ManNAc in subjects with GNE myopathy.

ManNAc, the first committed precursor for the biosynthesis of Neu5Ac (sialic acid), and a substrate of the GNE enzyme defective in GNE myopathy, is being developed for this orphan indication. A first-in- human Phase 1 trial has been completed and an Open-Label Phase 2 trial is ongoing. NN109 is a randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of ManNAc in subjects with GNE myopathy. We hope that this study will inform future trials and will eventually lead to FDA approval for ManNAc in GNE myopathy.

The primary efficacy endpoint and design this trial in 50 GNE myopathy subjects is based on knowledge collected for 5 years as part of an ongoing natural history study (NCT01417533; PI: Dr. Nuria Carrillo) which led to the development of the GNE Myopathy Disease Progression Model. This disease progression model is a novel tool that has allowed the design of a trial that overcomes the challenges of determining treatment effect in this rare and slowly progressive disease. The disease progression model facilitates recruitment of subjects within a wide range of the disease spectrum, increasing the generalizability of our findings to the patient population. Furthermore, our strategy could be applied to other slowly progressive muscle diseases. Finally, we hope that our trial and patient recruitment efforts will increase awareness of GNE myopathy and identification of undiagnosed patients.

The objective of NN109 is to evaluate the efficacy of ManNAc in subjects with BNE myopathy as measured by ability to slow progression of muscle decline compared to placebo.

NN109 is supported by NIAMS and NINDS (U01 AR070498) and includes a partnership with Berry Consultants.

Protocol Principal Investigator: 
Contact Information: 

CCC Project Manager: David Klements, Kadine SolomonBrenda Thornell

DCC Project Coordinators: Cynthia DiltzJulie Qidwai