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Abstract: TH-PO365

Efficacy and Safety of Oxabact® OC5 in Dialysis Patients with Primary Hyperoxaluria Type 1 (PH1): A Phase II, Prospective, Open-Label Study

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Hoppe, Bernd, University Hospital Bonn, Bonn, Germany
  • Dehmel, Bastian, OxThera AB, Thousand Oaks, California, United States
  • Herberg, Ulrike, University of Bonn, Bonn, Germany
Background

In PH1, endogenous overproduction of oxalate in the liver and, therefore, extremely elevated urinary oxalate excretion lead to early end-stage renal disease with patients requiring dialysis and/or liver (±kidney transplantation). Removal of oxalate via dialysis is insufficient and cannot match the endogenous production. Oxabact®, a formulation of an oxalate-metabolizing bacterium (Oxalobacter formigenes), induces active secretion of oxalate in the intestinal lumen and generates reductions in plasma and urinary oxalate (Pox and Uox, respectively) in patients with PH1 at various stages of renal impairment. This Phase II, prospective, open-label study investigated efficacy and safety of an improved Oxabact® formulation, OC5, in patients with PH1 treated with a stable dialysis regimen.

Methods

After a 4-week baseline period, patients received OC5 (one oral capsule containing ≥109 CFU lyophilized O.formigenes, twice a day) for 6 weeks and were monitored for an additional 4 weeks (initial treatment), before they started an extended treatment at the same dose until transplantation or a maximum of 36 months. Total and free Pox were evaluated monthly. Traditional and Speckle-Tracking Echocardiography were performed at baseline and then every 6 months. Fecal analyses for O. formigenes and standard safety assessments were conducted. This is the interim analysis of the study’s first 12 months.

Results

To date, 12 subjects have been enrolled and six subjects with a mean (SD) age of 30.5 (14.0) years have received OC5 for up to 12 months. Total Pox (mean at baseline 153.48 µmol/L, maximum mean decrease: 43.52 μmol/L at Week 44) and total:free Pox ratio (mean at baseline 1.468, 1.223 at Week 52; p <0.05) decreased. Cardiac parameters clearly indicated that systemic oxalosis did not worsen under treatment. O.formigenes genotype 1 was detectable in all patients. Six subjects reported 52 adverse events; most were mild or moderate (88.5%) and not related (90.4%) to treatment. Two subjects experienced serious adverse events, unrelated to treatment.

Conclusion

A 52-week treatment regimen with OC5 in patients with PH1 undergoing dialysis was safe, reduced Pox, and provided evidence that systemic oxalate deposition was attenuated, which would be of a substantial clinical significance for future transplantation outcome.

Funding

  • Commercial Support