Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy
Rattachement africain : ru. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab. AIM: To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH. MATERIALS AND METHODS: The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks. RESULTS: During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity. CONCLUSION: The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy
- Date Crossref
- 01/09/2020
- Éditeur
- Consilium Medicum
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Botkin Hospital pays non établi dans la noticeÉtablissement de santé
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City Clinical Hospital pays non établi dans la noticeÉtablissement de santé
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First Pavlov State Medical University of St. Petersburg pays non établi dans la noticeUniversité ou école supérieure
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Samara State Medical University pays non établi dans la noticeUniversité ou école supérieure
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Regional Children's Hospital No1 pays non établi dans la noticeÉtablissement de santé
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Kirov Research Institute of Hematology and Blood Transfusion FMBA pays non établi dans la noticeÉtablissement de santé
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Generium Pharmaceuticals (Russia) pays non établi dans la noticeEntreprise
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Pavlov First Saint Petersburg State Medical University pays non établi dans la noticeUniversité ou école supérieure
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National Hematology Medical Research Center pays non établi dans la noticeStructure de recherche
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Sverdlovsk Regional Clinical Hospital №1 pays non établi dans la noticeÉtablissement de santé
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Rostov Regional Clinical Hospital pays non établi dans la noticeÉtablissement de santé
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JSC GENERIUM pays non établi dans la noticeInstitution
Botkin Hospital, City Clinical Hospital et First Pavlov State Medical University of St. Petersburg, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.