CLINICAL STUDIES

Clinical studies with Oxabact® have been performed with both earlier formulations and with the high-dose Oxabact® OC5 product. Overall, Oxabact® has been safely tested and was well tolerated in over 100 patients with primary Hyperoxaluria.

Initial Development Path

Earlier studies with Oxabact® showed a substantial decrease in urinary oxalate excretion in subjects with PH. A compelling reduction of urinary oxalate was accepted as a surrogate endpoint for evaluating the efficacy in PH. Several subsequent trials with this formulation failed to reach the primary endpoint, most likely because the patient population enrolled was too heterogeneous and the studies were too short. It was also determined that the formulation used in these studies had a low viable cell count and slow recovery rate of the bacteria once released in the intestinal tract. Drug manufacturing changes resulted in an improved and highly concentrated Oxabact® OC5 product. OC5 has a higher viable cell count and faster recovery from the freeze-dried state than its predecessors. Several other improvements in the manufacturing process were also made.

Oxabact® OC5 product has been used in all clinical trial since late 2013. OC5 treatment has been associated with a statistically significant increase in the number of O. formigenes cells in the feces of patients compared with placebo. This demonstrated that O. formigenes had been successfully delivered to the gut.

Study with Oxabact® OC5 in high risk dialysis patients

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In May 2014, OxThera initiated a study in PH patients with ESRD on dialysis. The trial is currently ongoing in Germany. This open-label study was initially a 14-week study (4 weeks baseline, 6 weeks treatment with OC5 and 4 weeks post treatment). However, the initial 6-week treatment period was too short to see a relevant change in plasma oxalate concentrations. The treatment period subsequently was amended to a duration up to 36 months or transplantation, whichever occurred earlier.

As of December 2018, 12 patients have been treated with OC5 in the OC5-OL-01 study. An interim analysis of the first 6 patients reaching the 12 month treatment milestone demonstrated a clinically relevant reduction of total plasma oxalate (Pox) of about 20% across 52 weeks of treatment together with a stabilisation of free (soluble) Pox. No subject had an increase in Pox concentration at the one-year mark, a remarkable finding considering that dialysis frequency was not increased.

In this study, cardiac function was determined at baseline and over time using traditional, and Speckle Tracking echocardiography. The one-year results indicate an improvement in left-ventricular function across the study population. This could be an indicator that treatment with OC5 reduces systemically deposited calcium oxalate deposists and ameliorates cardiac function. The safety profile has been favorable and OC5 was well tolerated by patients in the study. To date, no drug-related serious adverse events have been reported for Oxabact®.

While the efficacy outcome for previous studies with Oxabact® differed, all clinical studies showed that oral administration of O. formigenes was safe and well tolerated.

ePHex Trial – Phase III Clinical Study

The ongoing OC5-DB-02 study evaluates the effect of Oxabact® OC5 in PH patients with maintained renal function but with an eGFR below the lower limit of the normal range (<90 ml/min/1.73 m2) and an elevated Pox concentration. This is a phase III, double-blind, placebo-controlled study and subjects are being randomized 1:1 to receive either OC5 or placebo.

For more information visit clinicaltrials.gov.