A Study in MPS VI to Assess Safety and Efficacy of Odiparcil

Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs). Medical need for treatment of MPS is still very high due to the poor penetration of the recombinant enzymes into the blood brain barrier as well as the ocular barriers and into tissues that are poorly vascularized, such as cartilages and bones. Odiparcil is an orally active compound that allows the synthesis of soluble glycosaminoglycans (GAGs), mainly chondroitin sulfate (CS) and dermatane sulfate (DS). The neosynthesized solubles GAGs are then excreted in urine. By diverting endogenous GAG synthesis to the synthesis of soluble odiparcil linked GAGs, odiparcil should decrease the intracellular pool of GAGs and consequently decrease the lysosomal GAG accumulation. The primary objective of the study is to assess the safety and efficacy of two doses of odiparcil in MPS VI patients and to provide evidence to enable the selection of the relevant dose of odiparcil for phase III study. The secondary objective of this study is to characterize the dose response, PK and PD of odiparcil.

Study design: This phase IIa study consists of 2 parts performed sequentially: a preliminary safety assessment followed by the core study with a double-blind, randomized, dose-ranged cohort of patients receiving Enzyme Replacement Therapy (ERT) and an open-label cohort of patients not receiving ERT. Preliminary safety assessment (N=2): open-label, escalating dose (2 doses) study. If acceptable safety profile is achieved, patients will be then included in the open-label arm of the core study. Core study Core study will be conducted on 2 populations in parallel: * A first cohort (N=18): MPS VI patients receiving ERT assigned in 3 arms: * Placebo (N=6) * Odiparcil 500 mg per day (250 mg BID) (N=6) * Odiparcil 1000 mg per day (500 mg BID) (N=6). * A second cohort (N=6): MPS VI patient not receiving ERT (odiparcil 1000 mg per day (500 mg BID)). Study duration: The overall study duration will be 20 months, including the 10-month enrolment period. For each patient, the study duration will be: * Preliminary safety assessment: 6 weeks including a 4-week run-in period followed by 2-week treatment period. Then, patients will go on treatment period in core study. * Core study: 34 weeks including a 4-week run-in period followed by 26-week treatment period and 4-week of follow-up.