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
Por:
Ariceta, G, Collard, L, Abroug, S, Moochhala, SH, Gould, E, Boussetta, A, Ben Hmida, M, De, S, Hunley, TE, Jarraya, F, Fraga, G, Banos, A, Lindner, E, Dehmel, B, Schalk, G
Publicada:
1 feb 2023
Ahead of Print:
1 may 2022
Resumen:
Background 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 (TM), a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH.
Methods 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(2)) 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 mu mol/L; 95% CI: - 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments.
Conclusions 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.
Filiaciones:
Ariceta, G:
Hosp Valle De Hebron, Barcelona, Spain
Collard, L:
Ctr Hosp Umniversitaire Liege, Liege, Belgium
Abroug, S:
Hop Univ Sahloul, Sousse, Tunisia
Moochhala, SH:
Royal Free Hosp, London, England
Gould, E:
Vanderbilt Univ Sch Med, Nashville, TN USA
Boussetta, A:
Charles Nicolle Univ Hosp, Tunis, Tunisia
Ben Hmida, M:
Hedi Chaker Univ Hosp, Sfax, Tunisia
De, S:
Nottingham Childrens Hosp, Nottingham, England
Hunley, TE:
Vanderbilt Univ Sch Med, Nashville, TN USA
Jarraya, F:
Hedi Chaker Univ Hosp, Sfax, Tunisia
Fraga, G:
Hosp Valle De Hebron, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Banos, A:
OxThera Intellectual Property AB, Stockholm, Sweden
Lindner, E:
OxThera Intellectual Property AB, Stockholm, Sweden
Dehmel, B:
OxThera Intellectual Property AB, Stockholm, Sweden
Schalk, G:
Kindernierenzentrum, Bonn, Germany
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