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

Idiopathic Thrombocytopenic Purpura Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05220878
• Other study ID #: RMP-ITP-III
• Secondary ID: ? 407 eff. date
• Status: Completed
• Phase: Phase 3
• Start date: September 9, 2021
• Est. completion date: October 19, 2023

Study information

• Verified date: March 2024
• Source: AO GENERIUM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: October 19, 2023
• Est. primary completion date: August 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Idiopathic Thrombocytopenic Purpura
• Purpura
• Purpura, Thrombocytopenic
• Purpura, Thrombocytopenic, Idiopathic

Intervention

Biological:
• GNR-069
Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.
• Nplate
Once a week as a subcutaneous injection. The initial dose is 1 mcg/kg.

Locations

Country	Name	City	State
Russian Federation	Municipal budgetary institution "Central City Hospital No. 7"	Ekaterinburg
Russian Federation	State Budgetary Institution of Healthcare Irkutsk awarded the "Sign of Honor" Order Regional Clinical Hospital	Irkutsk	Irkutsk Region
Russian Federation	State Budgetary Health Institution of the Kaluga Region "Kaluga Regional Clinical Hospital"	Kaluga	Kaluga Region
Russian Federation	State Autonomous Healthcare Institution "Kuzbass Clinical Hospital named after S.V. Belyaev"	Kemerovo	Kemerovo Region
Russian Federation	Federal State Budgetary Institution "National Medical Research Center for Hematology" of the Ministry of Health of the Russian Federation	Moscow
Russian Federation	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	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	State Budgetary Health Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"	Moscow
Russian Federation	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	Llc "Medis"	Nizhny Novgorod	Nizhny Novgorod Region
Russian Federation	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	Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation	Novosibirsk	Novosibirsk Region
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation	Rostov-on-Don	Rostov Region
Russian Federation	Federal State Budgetary Institution "National Medical Research Center named after V.A. Almazov" of the Ministry of Health of the Russian Federation	Saint Petersburg
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation	Samara	Samara Region
Russian Federation	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	Saratov	Saratov Region
Russian Federation	State Health Institution of the Tula Region "Tula Regional Clinical Hospital"	Tula	Tula Region
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation	Ufa	Republic Of Bashkortostan

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time from initiation of therapy with investigational or reference drug to reaching a stable platelet count		26 weeks
Secondary	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
Secondary	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
Secondary	Change in ITP-specific bleeding assessment tool (ITP-BAT) scores at last visit from baseline at screening		26 weeks
Secondary	Proportion of patients with no/loss of response to treatment with investigational or reference drug		26 weeks
Secondary	Proportion of patients receiving approved ITP prophylactic drugs (glucocorticosteroids, azathioprine, danazol) in this study at the time of randomization		26 weeks