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

Study Overview

• Status: Completed
• Conditions: Idiopathic Thrombocytopenic Purpura
• Intervention / Treatment: Biological: GNR-069; Biological: Nplate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Ekaterinburg, Russian Federation, 620137
    • Municipal budgetary institution "Central City Hospital No. 7"
  • Moscow, Russian Federation, 127644
    • State budgetary health care institution of the city of Moscow "City Clinical Hospital named after V.V. Veresaev of the Department of Health of the City of Moscow"
  • Moscow, Russian Federation, 111123
    • State Budgetary Institution of Healthcare of the city of Moscow "Moscow Clinical Scientific and Practical Center named after A.S. Loginov" Department of Health of the city of Moscow.
  • Moscow, Russian Federation, 125167
    • Federal State Budgetary Institution "National Medical Research Center for Hematology" of the Ministry of Health of the Russian Federation
  • Moscow, Russian Federation, 125284
    • State budgetary health care institution of the city of Moscow "Clinical Hospital named after S.P. Botkin" of the Department of Health of the city of Moscow
  • Moscow, Russian Federation, 129110
    • State Budgetary Health Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"
  • Saint Petersburg, Russian Federation, 197341
    • Federal State Budgetary Institution "National Medical Research Center named after V.A. Almazov" of the Ministry of Health of the Russian Federation
  • Irkutsk Region
    • Irkutsk, Irkutsk Region, Russian Federation, 664079
      • State Budgetary Institution of Healthcare Irkutsk awarded the "Sign of Honor" Order Regional Clinical Hospital
  • Kaluga Region
    • Kaluga, Kaluga Region, Russian Federation, 248007
      • State Budgetary Health Institution of the Kaluga Region "Kaluga Regional Clinical Hospital"
  • Kemerovo Region
    • Kemerovo, Kemerovo Region, Russian Federation, 650066
      • State Autonomous Healthcare Institution "Kuzbass Clinical Hospital named after S.V. Belyaev"
  • Nizhny Novgorod Region
    • Nizhny Novgorod, Nizhny Novgorod Region, Russian Federation, 603126
      • State budgetary institution of health care of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N. A. Semashko"
    • Nizhny Novgorod, Nizhny Novgorod Region, Russian Federation, 603137
      • Llc "Medis"
  • Novosibirsk Region
    • Novosibirsk, Novosibirsk Region, Russian Federation, 630091
      • Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
  • Republic Of Bashkortostan
    • Ufa, Republic Of Bashkortostan, Russian Federation, 450008
      • Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
  • Rostov Region
    • Rostov-on-Don, Rostov Region, Russian Federation, 344022
      • Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation
  • Samara Region
    • Samara, Samara Region, Russian Federation, 443099
      • Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
  • Saratov Region
    • Saratov, Saratov Region, Russian Federation, 410012
      • Federal State Budgetary Educational Institution of Higher Education "Saratov State Medical University named after V.I. Razumovsky" of the Ministry of Health of the Russian Federation
  • Tula Region
    • Tula, Tula Region, Russian Federation, 300053
      • State Health Institution of the Tula Region "Tula Regional Clinical Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Chair: Oksana A. Markova, MD, MSc, AO GENERIUM

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): October 19, 2023

Study Registration Dates

• First Submitted: January 21, 2022
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Bleeding; Haemorrhage; Platelets; romiplostim; ITP; Autoantibodies; T cells; Thrombocytopenia; Idiopathic thrombocytopenic purpura; Thrombocytopoiesis; 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; Platelet destruction; Impaired thrombopoiesis; Megakaryocytes; Splenectomy; Cytotoxic; Thrombopoietin receptor agonists; TPO-RAs; Nplate
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Cytopenia; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: RMP-ITP-III; № 407 eff. date 29 July 2021 (Other Identifier: Ministry of Health of the Russian Federation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No