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

Primary Purpose

Idiopathic Thrombocytopenic Purpura

Status
Recruiting
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
GNR-069
Nplate
Sponsored by
AO GENERIUM
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Thrombocytopenic Purpura focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • State Budgetary Institution of Healthcare Irkutsk awarded the "Sign of Honor" Order Regional Clinical Hospital
  • State Budgetary Health Institution of the Kaluga Region "Kaluga Regional Clinical Hospital"
  • State Autonomous Healthcare Institution "Kuzbass Clinical Hospital named after S.V. Belyaev"
  • State budgetary institution of health care of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N. A. Semashko"
  • Llc "Medis"
  • Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
  • Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
  • Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation
  • Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian FederationRecruiting
  • 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
  • State Health Institution of the Tula Region "Tula Regional Clinical Hospital"
  • Municipal budgetary institution "Central City Hospital No. 7"
  • 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.
  • Federal State Budgetary Institution "National Medical Research Center for Hematology" of the Ministry of Health of the Russian Federation
  • 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
  • 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"
  • State Budgetary Health Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"Recruiting
  • Federal State Budgetary Institution "National Medical Research Center named after V.A. Almazov" of the Ministry of Health of the Russian FederationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GNR-069

Nplate

Arm Description

Main group (80 patients) - multiple weekly subcutaneous injections of GNR-069, doses are calculated individually.

Control group (80 patients) - multiple weekly subcutaneous injections of Nplate, doses are calculated individually.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Time from initiation of therapy with investigational or reference drug to reaching a stable platelet count
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
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
Change in ITP-specific bleeding assessment tool (ITP-BAT) scores at last visit from baseline at screening
Proportion of patients with no/loss of response to treatment with investigational or reference drug
Proportion of patients receiving approved ITP prophylactic drugs (glucocorticosteroids, azathioprine, danazol) in this study at the time of randomization

Full Information

First Posted
January 21, 2022
Last Updated
February 22, 2023
Sponsor
AO GENERIUM
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1. Study Identification

Unique Protocol Identification Number
NCT05220878
Brief Title
Comparative Study of Clinical Efficacy and Safety of GNR-069 and Nplate in Patients With ITP
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
November 10, 2023 (Anticipated)
Study Completion Date
January 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AO GENERIUM

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Thrombocytopenic Purpura
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Parallel assignment
Masking
ParticipantInvestigator
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GNR-069
Arm Type
Experimental
Arm Description
Main group (80 patients) - multiple weekly subcutaneous injections of GNR-069, doses are calculated individually.
Arm Title
Nplate
Arm Type
Active Comparator
Arm Description
Control group (80 patients) - multiple weekly subcutaneous injections of Nplate, doses are calculated individually.
Intervention Type
Biological
Intervention Name(s)
GNR-069
Other Intervention Name(s)
romiplostim
Intervention Description
Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.
Intervention Type
Biological
Intervention Name(s)
Nplate
Other Intervention Name(s)
romiplostim
Intervention Description
Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.
Primary Outcome Measure Information:
Title
Proportion of patients achieving sustained response to treatment
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients who achieve stable platelet count during treatment with investigational or reference drug
Description
Stable platelet count is defined as the number of platelets ≥ 50.0 x 109/L for at least 4 consecutive weeks without dose adjustment.
Time Frame
26 weeks
Title
Time from initiation of therapy with investigational or reference drug to reaching a stable platelet count
Time Frame
26 weeks
Title
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
Time Frame
25 weeks
Title
Number of clinically significant bleeding episodes during the treatment period, starting from the second week of therapy with investigational or reference drug
Description
Bleeding episode ≥ Grade 2 according to CTCAE version 5.0 is considered clinically significant
Time Frame
26 weeks
Title
Change in ITP-specific bleeding assessment tool (ITP-BAT) scores at last visit from baseline at screening
Time Frame
26 weeks
Title
Proportion of patients with no/loss of response to treatment with investigational or reference drug
Time Frame
26 weeks
Title
Proportion of patients receiving approved ITP prophylactic drugs (glucocorticosteroids, azathioprine, danazol) in this study at the time of randomization
Time Frame
26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rusava O. Matyushina, MD, PhD
Phone
+79150880405
Email
romatyushina@generium.ru
First Name & Middle Initial & Last Name or Official Title & Degree
Oksana A. Markova, MD
Phone
+79854418959
Email
oamarkova@generium.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oksana A. Markova, MD, MSc
Organizational Affiliation
AO GENERIUM
Official's Role
Study Chair
Facility Information:
Facility Name
State Budgetary Institution of Healthcare Irkutsk awarded the "Sign of Honor" Order Regional Clinical Hospital
City
Irkutsk
State/Province
Irkutsk Region
ZIP/Postal Code
664079
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
State Budgetary Health Institution of the Kaluga Region "Kaluga Regional Clinical Hospital"
City
Kaluga
State/Province
Kaluga Region
ZIP/Postal Code
248007
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
State Autonomous Healthcare Institution "Kuzbass Clinical Hospital named after S.V. Belyaev"
City
Kemerovo
State/Province
Kemerovo Region
ZIP/Postal Code
650066
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
State budgetary institution of health care of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N. A. Semashko"
City
Nizhny Novgorod
State/Province
Nizhny Novgorod Region
ZIP/Postal Code
603126
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
Llc "Medis"
City
Nizhny Novgorod
State/Province
Nizhny Novgorod Region
ZIP/Postal Code
603137
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
City
Novosibirsk
State/Province
Novosibirsk Region
ZIP/Postal Code
630091
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
City
Ufa
State/Province
Republic Of Bashkortostan
ZIP/Postal Code
450008
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation
City
Rostov-on-Don
State/Province
Rostov Region
ZIP/Postal Code
344022
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
City
Samara
State/Province
Samara Region
ZIP/Postal Code
443099
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
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
City
Saratov
State/Province
Saratov Region
ZIP/Postal Code
410012
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
State Health Institution of the Tula Region "Tula Regional Clinical Hospital"
City
Tula
State/Province
Tula Region
ZIP/Postal Code
300053
Country
Russian Federation
Individual Site Status
Enrolling by invitation
Facility Name
Municipal budgetary institution "Central City Hospital No. 7"
City
Ekaterinburg
ZIP/Postal Code
620137
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
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.
City
Moscow
ZIP/Postal Code
111123
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
Federal State Budgetary Institution "National Medical Research Center for Hematology" of the Ministry of Health of the Russian Federation
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
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
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
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"
City
Moscow
ZIP/Postal Code
127644
Country
Russian Federation
Individual Site Status
Not yet recruiting
Facility Name
State Budgetary Health Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Individual Site Status
Recruiting
Facility Name
Federal State Budgetary Institution "National Medical Research Center named after V.A. Almazov" of the Ministry of Health of the Russian Federation
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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