Clinical trial NCT05220878: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2022-02-02
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients achieving sustained response to treatment
timeFrame: 26 weeks
Secondary outcomes:
measure: Proportion of patients who achieve stable platelet count during treatment with investigational or reference drug
timeFrame: 26 weeks
measure: Time from initiation of therapy with investigational or reference drug to reaching a stable platelet count
timeFrame: 26 weeks
measure: 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
timeFrame: 25 weeks
measure: Number of clinically significant bleeding episodes during the treatment period, starting from the second week of therapy with investigational or reference drug
timeFrame: 26 weeks
measure: Change in ITP-specific bleeding assessment tool (ITP-BAT) scores at last visit from baseline at screening
timeFrame: 26 weeks
measure: Proportion of patients with no/loss of response to treatment with investigational or reference drug
timeFrame: 26 weeks
measure: Proportion of patients receiving approved ITP prophylactic drugs (glucocorticosteroids, azathioprine, danazol) in this study at the time of randomization
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Irkutsk
country: Russian Federation
facility: State Budgetary Institution of Healthcare Irkutsk awarded the "Sign of Honor" Order Regional Clinical Hospital
state: Irkutsk Region
city: Kaluga
country: Russian Federation
facility: State Budgetary Health Institution of the Kaluga Region "Kaluga Regional Clinical Hospital"
state: Kaluga Region
city: Kemerovo
country: Russian Federation
facility: State Autonomous Healthcare Institution "Kuzbass Clinical Hospital named after S.V. Belyaev"
state: Kemerovo Region
city: Nizhny Novgorod
country: Russian Federation
facility: State budgetary institution of health care of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Hospital named after N. A. Semashko"
state: Nizhny Novgorod Region
city: Nizhny Novgorod
country: Russian Federation
facility: Llc "Medis"
state: Nizhny Novgorod Region
city: Novosibirsk
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation
state: Novosibirsk Region
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
state: Republic Of Bashkortostan
city: Rostov-on-Don
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University" of the Ministry of Health of the Russian Federation
state: Rostov Region
city: Samara
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
state: Samara Region
city: Saratov
country: Russian Federation
facility: 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: Saratov Region
city: Tula
country: Russian Federation
facility: State Health Institution of the Tula Region "Tula Regional Clinical Hospital"
state: Tula Region
city: Ekaterinburg
country: Russian Federation
facility: Municipal budgetary institution "Central City Hospital No. 7"
city: Moscow
country: Russian Federation
facility: 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
country: Russian Federation
facility: Federal State Budgetary Institution "National Medical Research Center for Hematology" of the Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: 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
country: Russian Federation
facility: 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
country: Russian Federation
facility: State Budgetary Health Institution of the Moscow Region "Moscow Regional Research Clinical Institute named after M.F. Vladimirsky"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "National Medical Research Center named after V.A. Almazov" of the Ministry of Health of the Russian Federation
Study officials:
affiliation: AO GENERIUM
name: Oksana A. Markova, MD, MSc
role: STUDY_CHAIR
References: