Clinical trial NCT06497036: Study of Efficacy, Safety and Immunogenicity of GP40141 (GEROPHARM, Russia) in Patients With Immune Thrombocytopenia
Official title: Multicenter Randomized Controlled Study of Efficacy, Safety and Immunogenicity of GP40141 (GEROPHARM, Russia) Compared With Nplate® (Amgen, the Netherlands) in Patients With Persistent or Early Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Drug Effect
Safety Issues
Immunogenicity
Keywords: romiplostim, nplate, bioequivalence
Lead sponsor: Geropharm
Sponsor class: INDUSTRY
Collaborators: name: Pharm-Holding
name: I.M. Sechenov First Moscow State Medical University
First posted: 2024-07-11
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, single-blind, randomized controlled trial of efficacy and safety in two parallel groups
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Proportion of subjects with platelet response
timeFrame: 10 weeks
measure: Number of adverse events (AEs)
timeFrame: 10 weeks
measure: Proportion of subjects experiencing AEs,
timeFrame: 10 weeks
measure: Proportion subjects with a immune response to romiplostim
timeFrame: 26 weeks
measure: Proportion subjects with a immune response to endogenous thrombopoietin
timeFrame: 26 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Kaluga
country: Russian Federation
facility: Kaluga Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: City Clinical Hospital S.P. Botkin of the Moscow City Health Department
city: Saint-Petersburg
country: Russian Federation
facility: National Medical Research Center in name of V.A. Almazov " of the Ministry of Health of the Russian Federation
city: Samara
country: Russian Federation
facility: Samara State Medical University" of the Ministry of Health of the Russian Federation
city: Sochi
country: Russian Federation
facility: Oncological dispensary No. 2 of the Ministry of Health of the Krasnodar Territory
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution Bashkir State Medical University of the Ministry of Health of the Russian Federation
Study officials:
affiliation: Bashkir State Medical University of the Ministry of Health of the Russian Federation
name: Bulat Bakirov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaluga Regional Clinical Hospital
name: Elena Borisenkova
role: PRINCIPAL_INVESTIGATOR
affiliation: City Clinical Hospital named after S.P. Botkin of the Moscow City Health Department
name: Olga Vinogradova
role: PRINCIPAL_INVESTIGATOR
affiliation: Samara State Medical University of the Ministry of Health of the Russian Federation
name: Igor Davydkin
role: PRINCIPAL_INVESTIGATOR
affiliation: Oncological dispensary No. 2 of the Ministry of Health of the Krasnodar Territory
name: Dmitry Kirtbaya
role: PRINCIPAL_INVESTIGATOR
affiliation: National Medical Research Center VA Almazov Ministry of Health of the Russian Federation
name: Galina Salogub
role: PRINCIPAL_INVESTIGATOR
References: