Drug Effect, Safety Issues, Immunogenicity
Conditions
Keywords
romiplostim, nplate, bioequivalence
Brief summary
The goal of this clinical trial is to demonstrate equivalent efficacy and comparable safety of the drug GP40141 (GEROPHARM, Russia) in comparison with the drug Nplate® (Amgen, the Netherlands). the main questions are 1. Assess the effectiveness of GP40141 in comparison with Nplate®. 2. Assess the immunogenicity of GP40141 in comparison with the drug Nplate®. 3. Assess the safety of GP40141 in comparison with the drug Nplate®. 4. Assess the safety of changing romiplostim and eltrombopag to GP40141. 5. Assess the pharmacokinetic parameters of the study drugs in patients with primary immune thrombocytopenia. Participants divided into 2 cohorts (naïve or treated with a thrombopoietin receptor agonist) will receive romiplostim and platelet response, immune response and adverse reactions will be assessed.
Detailed description
The study will be conducted in adult patients with persistent or chronic primary immune thrombocytopenia. Patients both naïve to treatment with a thrombopoietin receptor agonist (cohort 1) and those who have previously received therapy (cohort 2) will be included. Cohort 1: Adult steroid-dependent or steroid-refractory patients with persistent or chronic primary immune thrombocytopenia (PIT) with or without a history of splenectomy who have not previously received thrombopoietin receptor agonist (TPO-RA) therapy. Cohort 2: Adult patients with persistent or chronic primary immune thrombocytopenia receiving TPO-RA (romiplostim or eltrombopag) for ≥12 weeks and with sustained response status at screening.
Interventions
DRUGGP404141
subcutaneous injection
DRUGNplate
subcutaneous injection
Sponsors
Pharm-Holding
I.M. Sechenov First Moscow State Medical University
Geropharm
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
patients will not have access to the treatment assignment code and, therefore, will not know which study drug they are receiving
Intervention model description
Multicenter, single-blind, randomized controlled trial of efficacy and safety in two parallel groups
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent to participate in the study. * male or female * Age ≥18 years * Diagnosis of primary immune thrombocytopenia (PIT). * Duration of PIT at the Screening Visit: for cohort 1: ≥3 months; for cohort 2: ≥6 months. * PIT therapy with glucocorticosteroids (GCS) for cohort 1: duration of continuous therapy ≥3 months at the Screening Visit or ≥2 courses of pulse therapy during the year before the Screening Visit; * TPO-RA therapy: for cohort 1: no history of TPO-RA use; for Cohort 2: Use of TPO-RA for ≥12 weeks at the Screening Visit; * No increase in TPO-RA dose during the 4 weeks preceding the end of screening. * Blood platelet count: for cohort 1: mean platelet count ≤30×10\*9/L, based on the last two measurements 7±2 days apart, each of which had a platelet count ≤35×10\*9/L OR steroid dependence, defined as the use of prednisolone at a daily dose of \>5 mg (or another corticosteroid at an equivalent dose) for ≥2 months before the Screening Visit to maintain a platelet count ≥30×10\*9/L OR to prevent bleeding; for cohort 2: platelet count ≥50×10\*9/ml for ≥6 weeks out of the last 8 weeks of follow-up with platelet counts every 7±2 days and no emergency treatment for severe hemorrhagic syndrome in the last 12 weeks before the Screening Visit. * Consent and ability to comply with the procedures of the Protocol, as well as the prohibitions and restrictions provided for by the Research Protocol.
Exclusion criteria
* Hypersensitivity to romiplostim. * History of TPO-RA use: for cohort 1: any TPO-RA; for cohort 2: any TPO-RA, with the exception of romiplostim and eltrombopag. * Unpromising treatment with romiplostim in the opinion of the Researcher * Splenectomy \<24 weeks prior to the Screening Visit or planned splenectomy during the study. * Treatment with rituximab within the 14 weeks preceding the Screening Visit, or planned treatment with rituximab during the study. * Treatment with intravenous immunoglobulin or anti-D immunoglobulin during the 2 weeks preceding the Screening Visit, or planned use during the study. * Therapy with hematopoietic growth factors during the 4 weeks preceding the Screening Visit, or their planned use during the study. * Therapy with alkylating chemotherapy drugs during the 8 weeks preceding the Screening Visit, or their planned use during the study. * Use of other medicines listed in section 5.3.3. of this study protocol. * Participation in a clinical trial of an investigational drug or investigational medical device within 4 weeks or 5 half-lives (whichever is longer) preceding the Screening Visit. * Secondary immune thrombocytopenia in the following diseases: autoimmune thyroiditis, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), lymphoproliferative diseases, drug-mediated, viral origin (herpes viruses, HIV, chronic viral hepatitis). * Hereditary thrombocytopenia. * Diseases of the hematopoietic system accompanied by thrombocytopenia (for example, acute leukemia, aplastic anemia, myelodysplastic syndrome, lymphoproliferative diseases). * Metastatic bone marrow lesions. * Uncontrolled concomitant diseases of internal organs. * Arterial thrombosis (for example, myocardial infarction, acute cerebrovascular accident) within 1 year preceding the Screening Visit. * History of venous thrombosis. * High risk of venous thrombosis and thromboembolism, defined as the presence of at least three of the following risk factors: * diabetes; * smoking; * use of combined oral contraceptives or menopausal hormone therapy; * positive titer of antiphospholipid antibodies; * hypercholesterolemia (\>240 mg/dl or \>13 mmol/l); * hypertriglyceridemia; * arterial hypertension requiring therapy. * HIV infection. * Viral hepatitis B or C. * Oncological and/or oncohematological disease beyond the stage of complete 5-year remission at the Screening Visit. * Major surgery (major surgery) within 8 weeks preceding the Screening Visit, or incomplete recovery from surgery at the Screening Visit. * Pregnancy or lactation in women. * Hospitalization for any reason planned during the patient's participation in the study. * A history of mental disorders that do not allow you to adequately assess your behavior and follow the conditions of the study protocol. * Alcoholism. Alcoholism or consumption of alcohol in quantities exceeding for men: 14 units. per week (on average); for women: 7 units. per week (on average).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with platelet response | 10 weeks | Blood platelet count ≥50×10\*9/L after 10 weeks of therapy (at Visit 11), or blood platelet count ≥200×10\*9/L at the last assessment if the study was terminated early. |
| Number of adverse events (AEs) | 10 weeks | AEs including ones of special interest: bleeding, thrombotic and thromboembolic events. |
| Proportion of subjects experiencing AEs, | 10 weeks | AEs including ones of special interest: bleeding, thrombotic and thromboembolic events. |
| Proportion subjects with a immune response to romiplostim | 26 weeks | Proportion of initially immunonaive subjects with a documented immune response to romiplostim at Visits 8 and 26 (weeks 8 and 26). |
| Proportion subjects with a immune response to endogenous thrombopoietin | 26 weeks | Proportion of initially immunonaive subjects with a documented immune response to endogenous thrombopoietin at Visits 8 and 26 (weeks 8 and 26). |
Countries
Russia
Outcome results
None listed