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A randomised Phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria

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Abstract

Background

Primary hyperoxaluria (PH) is a rare, genetic disorder which involves the overproduction of endogenous oxalate, leading to hyperoxaluria, recurrent urolithiasis and/or progressive nephrocalcinosis and eventually resulting in kidney failure and systemic oxalosis. The aim of this trial was to investigate whether treatment involving an oxalate-metabolising bacterium (Oxalobacter formigenes) could reduce urinary oxalate excretion in PH patients.

Methods

The efficacy and safety of O. formigenes (Oxabact® OC5; OxThera AB, Stockholm, Sweden) was evaluated in a randomised, placebo-controlled, double-blind study for 8 weeks. The primary objective was reduction in urinary oxalate excretion (Uox). Secondary objectives included faecal O. formigenes count and decrease in plasma oxalate concentration (Pox).

Results

Twenty-eight patients randomised 1:1 to the treatment group (OC5) or the placebo group completed the study. After 8 weeks of treatment, there was no significant difference in the change in Uox (mmol/24 h/1.73 m2) between the groups (OC5: +0.042, placebo: −0.140). Post-hoc analysis showed a statistically significant increase in Uox per urinary creatinine excretion in the OC5 group (OC5: +5.41, placebo: −15.96; p = 0.030). Change in Pox from baseline was not significantly different between groups (p = 0.438). The O. formigenes cell count was significantly increased in OC5-treated patients (p < 0.001) versus placebo. The treatment response to O. formigenes was related to individual stage of kidney deterioration, and Pox was directly correlated to kidney function, even for early-stage patients (chronic kidney disease stage 1). No safety issues were observed.

Conclusions

Treatment with OC5 did not significantly reduce Uox or Pox over 8 weeks of treatment. The treatment was well tolerated and successfully delivered to the gastrointestinal tract.

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Acknowledgements

The Department of Clinical Biochemistry at University College London Hospital, the Departments of Clinical Chemistry and Pediatrics at the Academic Medical Center, Amsterdam and the Institute for Microecology, Herborn were the central laboratories in this study. The investigators would also like to thank all of the patients who participated in this study. Medical writing services were paid for by OxThera and were provided by Drs James Serginson and Antigoni Ekonomou of Niche Science and Technology Limited.

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Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Nephrology, University Hospital Bonn, Adenauerallee 119, D-53113, Bonn, Germany

    Bernd Hoppe

  2. Pediatric Nephrology, Necker Hospital, Université Paris-Descartes, Paris, France

    Patrick Niaudet & Rémi Salomon

  3. Centre de référence Maladies Rénales Rares du Sud-Ouest, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

    Jérôme Harambat

  4. Department of Paediatric Nephrology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK

    Sally-Anne Hulton

  5. Renal Unit, Great Ormond Street Hospital, London, UK

    William Van’t Hoff

  6. UCL Centre for Nephrology, Royal Free Campus and Hospital, London, UK

    Shabbir H. Moochhala

  7. Pediatric Nephrology Department, Robert Debré Hospital, Paris, France

    Georges Deschênes

  8. OxThera AB, Stockholm, Sweden

    Elisabeth Lindner & Anna Sjögren

  9. Centre de référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Bron, France

    Pierre Cochat

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  1. Bernd Hoppe
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Corresponding author

Correspondence to Bernd Hoppe.

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Funding

The study was funded by OxThera Intellectual Property AB, Stockholm, Sweden.

This research has also received funding from the European Union’s Seventh Framework Programme managed by REA-Research Executive Agency http://ec.europa.eu/research/rea (FP7/2007–2013) under grant agreement no FP7-SME-2013.

Conflict of interest

Anna Sjögren and Elisabeth Lindner are employees at OxThera, the sponsor of the study. Bernd Hoppe has received consulting fees from OxThera.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Hoppe, B., Niaudet, P., Salomon, R. et al. A randomised Phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria. Pediatr Nephrol 32, 781–790 (2017). https://doi.org/10.1007/s00467-016-3553-8

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  • DOI: https://doi.org/10.1007/s00467-016-3553-8

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