iMProveS, a phase IIa study in adolescent and adult MPS VI patients
The 26-week Phase IIa clinical trial included 20 patients aged 16 years or older suffering from MPS VI. 15 patients were randomized in a double-blind, placebo-controlled cohort and received an oral dose of 250mg or 500mg of odiparcil or placebo twice a day for six months, in addition to enzyme replacement therapy (ERT), the current standard of care. The remaining five patients were included in an open-label cohort and received an oral dose of 500mg of odiparcil twice a day for six months, without being treated with ERT. 13 patients completed the study: four patients who received placebo in addition to ERT and nine patients equally distributed in each of the three odiparcil groups.
The clinical study met its safety primary objective further supporting the good overall safety profile of odiparcil already observed in previous Phase I and Phase II clinical studies conducted for the prevention of thrombosis. The majority of adverse events were mild or moderate. Compared to previous Phase I and II clinical studies conducted with odiparcil for the prevention of thrombosis, no new safety findings were observed.
Considering the short study duration and the advanced status of the disease in patients included in the study, the iMProveS study showed positive results regarding the efficacy of odiparcil:
− Improvements were observed in patients treated with odiparcil, in addition to ERT, with regards to corneal clouding as well as cardiac and respiratory functions.
− Consistent with odiparcil’s mechanism of action, a dose-dependent urinary clearance of glycosaminoglycans (GAGs), used as an activity biomarker, was clearly demonstrated in the entire patient population treated with odiparcil.
Results from the pharmacokinetics analysis were in line with expectations and will be used for dose selection in the next study planned with MPS VI children (Safe-KIDDS). In the iMProveS study, the pharmacokinetic profile obtained in MPS VI patients treated with odiparcil is not impacted by ERT and is consistent with profiles previously observed in Phase I and Phase II studies in prevention of thrombosis.
Patients who completed the iMProveS study will be offered to enter into a long-term follow-up extension study.
Additional clinical safety data
Odiparcil has undergone phase I and II clinical studies in post-operative deep-vein thrombosis and was found to be safe and well tolerated. More than 700 healthy volunteers received odiparcil in 29 completed phase I clinical pharmacology and pharmacokinetics studies. In these studies, employing single-doses and multiple-doses administered for up to 14 days, odiparcil was safe and well tolerated. Three phase IIb trials in the prevention of thromboembolism after hip arthroplasty or knee surgery and in patients at risk of a stroke were conducted using multiple-doses (250 to 1,000 mg/day) administered to more than 1200 patients for up to 16 weeks and confirmed odiparcil’s safety and tolerability.