title: A randomised Phase I/II trial to evaluate the efficacy and safety of orally administered Oxalobacter formigenes to treat primary hyperoxaluria.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, University Hospital Bonn, Adenauerallee 119, D-53113, Bonn, Germany. bernd.hoppe@ukb.uni-bonn.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
authors.affiliation: Pediatric Nephrology, Necker Hospital, Université Paris-Descartes, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.affiliation: Pediatric Nephrology, Necker Hospital, Université Paris-Descartes, Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.affiliation: Centre de référence Maladies Rénales Rares du Sud-Ouest, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Harambat
authors.affiliation: Department of Paediatric Nephrology, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Sally-Anne
authors.initials: SA
authors.lastname: Hulton
authors.affiliation: Renal Unit, Great Ormond Street Hospital, London, UK.
authors.forename: William
authors.initials: W
authors.lastname: Van't Hoff
authors.affiliation: UCL Centre for Nephrology, Royal Free Campus and Hospital, London, UK.
authors.forename: Shabbir H
authors.initials: SH
authors.lastname: Moochhala
authors.affiliation: Pediatric Nephrology Department, Robert Debré Hospital, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.affiliation: OxThera AB, Stockholm, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lindner
authors.affiliation: OxThera AB, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Sjögren
authors.affiliation: Centre de référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Bron, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
mesh_terms: D000293:Adolescent; D058491:Bacterial Load; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D006959:Hyperoxaluria / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D007677:Kidney Function Tests; D008297:Male; D019815:Oxalic Acid / Q000652:urine; D020624:Oxalobacter formigenes; D019936:Probiotics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D013608:Tablets, Enteric-Coated; D019815:Oxalic Acid
keywords: Kidney; Kidney function; Oxalate; Oxalobacter formigenes; Primary hyperoxaluria