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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Idiopathic Thrombocytopenic Purpura

Intervention / Treatment
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* Biological: GNR-069
* Biological: Nplate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent Form to participate in the study; Men and women aged 18-75 years inclusive at the time of signing the Informed Consent Form; 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; 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; 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; 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; 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: Hypersensitivity to the components of investigational or reference drug or E. coli proteins ; Unresolved severe hemorrhagic syndrome requiring emergency treatment at the time of initiation of study or reference drug therapy ; Fisher-Evans Syndrome; Conditions with a high risk of thromboembolic complications ; Myelodysplastic syndrome and/or bone marrow transplantation in anamnesis; Deviations of clinical and laboratory parameters according to the results of studies of blood samples taken during the screening period; Positive test results for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV); Pregnancy or breastfeeding; 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; Splenectomy within 12 weeks prior to screening; 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); Any other disease or condition that, in the opinion of the investigator, may preclude the patient from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GNR-069<br>Main group (80 patients) - multiple weekly subcutaneous injections of GNR-069, doses are calculated individually. | Biological: GNR-069<br>* Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.<br>* Other names: romiplostim;|
| Active Comparator: Nplate<br>Control group (80 patients) - multiple weekly subcutaneous injections of Nplate, doses are calculated individually. | Biological: Nplate<br>* Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.<br>* Other names: romiplostim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving sustained response to treatment | A sustained response to treatment is defined as the number of platelets ≥ 50.0 x 109/L for at least 9 out of 12 consecutive visits during the treatment period with the study or reference drug. | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve stable platelet count during treatment with investigational or reference drug | Stable platelet count is defined as the number of platelets ≥ 50.0 x 109/L for at least 4 consecutive weeks without dose adjustment. | 26 weeks | 
| Time from initiation of therapy with investigational or reference drug to reaching a stable platelet count |  | 26 weeks | 
| Number of cases of emergency therapy for severe hemorrhagic syndrome during the treatment period, starting from the second week of therapy with the investigational or reference drug |  | 25 weeks | 
| Number of clinically significant bleeding episodes during the treatment period, starting from the second week of therapy with investigational or reference drug | Bleeding episode ≥ Grade 2 according to CTCAE version 5.0 is considered clinically significant | 26 weeks | 
| Change in ITP-specific bleeding assessment tool (ITP-BAT) scores at last visit from baseline at screening |  | 26 weeks | 
| Proportion of patients with no/loss of response to treatment with investigational or reference drug |  | 26 weeks | 
| Proportion of patients receiving approved ITP prophylactic drugs (glucocorticosteroids, azathioprine, danazol) in this study at the time of randomization |  | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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