Comparative Study of Clinical Efficacy and Safety of GNR-069 and Nplate in Patients With ITP

Multicenter Randomized Double-blind Comparative Study of Clinical Efficacy and Safety of GNR-069 (JSC "GENERIUM", Russia) and Nplate (Amgen Europe BV, The Netherlands) in Patients With Idiopathic Thrombocytopenic Purpura

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.

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.