ePHex : a phase 3, double-blind, placebo-controlled, randomized study to evaluate long-term efficacy and safety of Oxalobacter formigenes in patients with primary hyperoxaluria
Ariceta Iraola, Gema (Hospital Universitari Vall d'Hebron)
Collard, L. (Centre Hospitalier Universitaire de Liège)
Abroug, S. (Hôpital Universitaire Sahloul)
Moochhala, S.H. (Royal Free Hospital)
Gould, E. (Vanderbilt University Hospital)
Boussetta, A. (Charles Nicolle University Hospital)
Ben Hmida, M. (Hedi Chaker University Hospital)
De, S. (Nottingham Children's Hospital)
Hunley, T.E. (Vanderbilt University Hospital)
Jarraya, F. (Hedi Chaker University Hospital)
Fraga, Gloria M. (Institut d'Investigació Biomèdica Sant Pau)
Banos, A. (OxThera Intellectual Property AB)
Lindner, E. (OxThera Intellectual Property AB)
Dehmel, B. (OxThera Intellectual Property AB)
Schalk, G. (Kindernierenzentrum)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH. Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1. 73 m) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint. Results: Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was - 3. 80 μmol/L; 95% CI: - 7. 83, 0. 23; p-value = 0. 064). Kidney function remained stable in both treatments. Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0. 06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Oxabact ; Oxalate ; Oxalobacter formigenes ; Primary hyperoxaluria ; Egfr
Publicat a:	Pediatric Nephrology, Vol. 38 Núm. 2 (february 2023) , p. 403-415, ISSN 1432-198X

DOI: 10.1007/s00467-022-05591-5
PMID: 35552824

13 p, 1.3 MB

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