comparative study of clinical efficacy and safety of gnr-069 and nplate in patients with itp

Conditions: Idiopathic Thrombocytopenic Purpura

Summary: it is a phase iii multicenter randomized double-blinded comparative study of clinical efficacy and safety of gnr-069 and nplate in patients with idiopathic thrombocytopenic purpura

the drug gnr-069(jsc "generium", russia) is biosimilar to the original drug nplate. this study is aimed to compare the clinical efficacy and safety of the drug gnr-069 and the drug nplate to register of the drug gnr-069 in the russian federation for therapy in patients with idiopathic thrombocytopenic purpura (itp). the study also provides for the evaluation of pharmacokinetic parameters and immunogenicity.

Eligibility criteria:
inclusion criteria: 1. written informed consent form to participate in the study; 2. men and women aged 18-75 years inclusive at the time of signing the informed consent form; 3. documented diagnosis of itp with a disease duration of more than 12 months from the moment of confirmation of the diagnosis by bone marrow aspirate or biopsy results; 4. a. for patients who have not had splenectomy: * established absence/loss of response to therapy with at least one drug of fist-line treatment for itp (which include gcs an ivig); or * the occurrence of side effects during the course of therapy with the drug of the fist-line, making it impossible to use it further; b. for patients who underwent splenectomy: • loss/lack of response to splenectomy; 5. thrombocytopenia ≥30.0 x 109/l - \<50.0 x 109/l with severe hemorrhagic syndrome or thrombocytopenia \<30.0 x 109/l, regardless of the presence of hemorrhagic syndrome, according to the results of platelet count conducted in a local laboratory for 7 days before the start of therapy with investigational or reference drug; 6. patients receiving gcs, azathioprine and danazole should receive these drugs in a maintenance dose for at least 4 weeks before starting therapy with investigational or reference drug; 7. consent of study participants with preserved childbearing function to use reliable methods of contraception (a combination of at least two methods, including 1 barrier method, for example, the use of a condom and spermicide) from the moment of signing the informed consent form and 3 months after the last administration of investigational or reference drug. exclusion criteria: 1. hypersensitivity to the components of investigational or reference drug or e. coli proteins ; 2. unresolved severe hemorrhagic syndrome requiring emergency treatment at the time of initiation of study or reference drug therapy ; 3. fisher-evans syndrome; 4. conditions with a high risk of thromboembolic complications ; 5. myelodysplastic syndrome and/or bone marrow transplantation in anamnesis; 6. deviations of clinical and laboratory parameters according to the results of studies of blood samples taken during the screening period; 7. positive test results for hepatitis b, hepatitis c, or human immunodeficiency virus (hiv); 8. pregnancy or breastfeeding; 9. use of drugs: * romiplostim used less than 3 weeks before treatment with study or reference drug; * ivig - less than 2 weeks prior to initiation of study or reference drug therapy; * eltrombopag - used less than 2 weeks before treatment with study or reference drug, or planned to use eltrombopag while the patient is participating in this study; * rituximab - used less than 14 weeks before treatment with study or reference drug, or planned to use rituximab while the patient is enrolled in this study; * cyclophosphamide, cyclosporine, vincristine, vinblastine and other drugs used to treat itp not listed above and not included in the list of drugs approved for use during the study - use less than 8 weeks before the start of therapy with the study or reference drug or the use of any of these drugs is planned during the patient's participation in this study; * preparations of any hematopoietic growth factors - use less than 8 weeks before the start of therapy with an investigational or reference drug; * influenza vaccines - less than 21 days prior to start of treatment with study or reference drug; * vaccines to prevent novel coronavirus disease (covid-19) - completion of the vaccination program less than 21 days prior to the start of study or reference drug therapy; * other vaccines - less than 8 weeks prior to start of treatment with study or reference drug; 10. splenectomy within 12 weeks prior to screening; 11. participation in any clinical trials and/or use of unregistered drugs within 4 weeks prior to screening or 5 drug half-lives (whichever is greater); 12. any other disease or condition that, in the opinion of the investigator, may preclude the patient from participating in the study.

Keywords: idiopathic thrombocytopenic purpura itp thrombocytopenia thrombocytopoiesis bleeding hemorrhagic syndrome petechial rash ecchymosis fc-peptide recombinant dna technology thrombopoietin receptors platelet formation fc fragment of human immunoglobulin igg 1 low platelet count itp treatment platelets haemorrhage platelet destruction impaired thrombopoiesis megakaryocytes autoantibodies splenectomy cytotoxic t cells thrombopoietin receptor agonists tpo-ras romiplostim nplate