Intravenous Immunoglobulin (IVIG, Bioven) Efficacy and Safety in Chronic Primary Immune Thrombocytopenia (ITP) in Adults

Study Overview
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Brief Summary
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The study will involve patients with chronic immune thrombocytopenia. This disease is diagnosed in the presence of isolated thrombocytopenia (decrease in platelet count only), except for other reasons. The addition of chronic means that the disease lasts more than 12 months. Patients included in the study will receive Bioven, 10% solution for infusion according to the protocol for the use of IVIG in ITP - at a dose of 0.8-1.0 g / kg 1 time per day for 2 consecutive days, the course dose of 1.6-2.0 g / kg according to the Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIG), rev. 3, 28 June 2018. After administration of the investigational drug, patients will be under medical supervision for 28 days. The stay of patients in the study - at least 4 weeks.

Detailed Description
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The investigational drug, IVIG, is used for immunomodulatory therapy in the treatment of autoimmune diseases. The study will involve patients with chronic immune thrombocytopenia. This autoimmune disease is diagnosed in the presence of isolated thrombocytopenia (decrease in platelet count only), except for other reasons. The addition of chronic means that the disease lasts more than 12 months. Screening stage The patient or her legal representative must sign an informed consent. After the informed consent signing procedure, the patient is screened and assessed for compliance with the inclusion and non-inclusion (exclusion) criteria. Clinical stage After the patient is included in the study, according to the protocol, he/she is hospitalized and the study drug is administered at a dose of 0.8-1.0 g/kg once a day for 2 days (the course dose is 1.6-2.0 g/kg). The next day after the administration of the drug, the patient undergoes blood sampling to determine the level of platelets, the level of immunoglobulin G (IgG) and the Coombs test. This procedure will also be carried out on days 7, 14, 21 and 28 after the first injection of the drug to monitor the patient's performance. The final stage The blood sampling procedure to determine the above indicators will be carried out on days 7, 14, 21, and 28 after the first administration of the drug to monitor the patient's performance.

Official Title
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Open, Multicenter, International Study to Evaluate the Efficacy, Safety and Tolerability of Bioven, Manufactured by Biopharma Plasma LLC, in Adult Patients With Chronic Primary Immune Thrombocytopenia (ITP)

Conditions
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Primary Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Intravenous immunoglobulin (IVIG), 10% solution for infusion


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed Patient Informed Consent Form for participation in the study; Men and women aged 18-65; Confirmed primary chronic ITP (lasting > 12 months since diagnosis); A full blood count should be normal except for the isolated thrombocytopenia. Patients with low hemoglobin levels (but above 90 g / l) may be included if there are symptoms of bleeding; If bleeding symptoms are diagnosed, the reticulocyte count should be measured; Platelet count <30 x 109 / L; If the patient is taking corticosteroids, the treatment regimen/dose should be stable (at least 2 weeks prior to screening); Negative pregnancy test (for women of child-bearing potential); Willingness to use effective and reliable methods of contraception throughout the entire study period; The results of physical, instrumental, and laboratory examination of patients should be within the normal range or deviations should be regarded by the researcher as clinically insignificant; Ability, according to the researcher, to follow all the requirements of the study protocol; Exclusion criteria: Known intolerance to plasma and immunoglobulin preparations; Drug allergy or hypersensitivity to immunoglobulin preparations; Confirmed deficiency of immunoglobulin A (IgA) and antibodies to IgA. Contraindications to immunoglobulin administration according to the instructions for medical use; Pregnancy and lactation; Any clinically significant hepatic impairment (increase of serum transaminase levels by more than 3 times the upper limit of normal); Serum creatinine levels are more than two times higher than the upper limit of normal for a given age and sex; Severe cardiovascular insufficiency (HF III); History of thrombosis or presence of significant risk factors for thrombosis. Patients with preventive splenectomy; Hemostatic disorders other than chronic thrombocytopenia; Persons with acute or exacerbation of chronic diseases of the gastrointestinal tract associated with the risk of bleeding, acute infectious diseases, pathologies of the respiratory system; Proven case of primary immunodeficiency; Secondary immune thrombocytopenia; Virus infections (Epstein-Barr, Cytomegalovirus, Parvovirus, Hepatitis B and C); Documented HIV infection Positive reaction of Wassermann (RW) test result; Systemic immunopathological diseases (rheumatic diseases, nephritis, etc.); Oncological diseases; Diabetes mellitus; Thyroid diseases; History of mental illness; Known drug addiction; Any other concomitant decompensated diseases or acute conditions, the presence of which, according to the researcher, may significantly affect the results of the study; The need to prescribe drugs that are incompatible with the administration of the drug in this study: other immunoglobulin preparations in addition to the study drug, cytostatic drugs, monoclonal antibodies, Avatrombopag); Experimental treatment (e.g. Rituximab therapy) for 3 months prior to screening); Blood transfusions or transfusions of blood products in the last 6 months prior to inclusion in the study; Administration of IVIG 30 days prior to screening; Participation in any other study currently or within the last 30 days; Criteria for exclusion of subjects (discontinuation of treatment with the study drug): Patient's wish Occurrence of severe and/or unexpected Adverse events (AE) or Adverse reactions (AR) in patient during the study, that require discontinuation of the drug; The need to prescribe drugs prohibited in this study. Significant deterioration of the patient's condition during the study period; Failure of the patient to adhere to the treatment regimen; Failure of the patient to follow the procedures established under the protocol;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open, multicenter, international, uncontrolled
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Main Group<br>Patients included in the study will receive the intravenous immunoglobulin (IVIG, Bioven), 10% solution for infusion according to the protocol for the use of IVIG in ITP treatment - at a dose of 0.8-1.0 g / kg once a day for 2 consecutive days, the course dose is 1.6-2.0 g / kg. The next day after the administration of the drug, the patient undergoes blood sampling to determine the level of platelets, the level of immunoglobulin G (IgG), and the Coombs test. This procedure will also be carried out on days 7, 14, 21, and 28 after the first injection of the drug to monitor the patient's performance. | Drug: Intravenous immunoglobulin (IVIG), 10% solution for infusion<br>* The study drug is administrated at a dose 0.8-1.0 g / kg once a day for 2 consecutive days, the course dose is 1.6-2.0 g / kg.<br>* Other names: Bioven, 10% solution for infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part (percent) of patients with response (R) | platelet count >30 x 109 /l and at least 2-fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and absence of bleeding | 28 days after first administration of the study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part (percent) of patients with complete response (CR) | platelet count >100 x 109 /l, confirmed on at least 2 separate occasions at least 7 days apart, and absence of bleeding | 28 days after first administration of the study drug | 
| Part (percent) of patients with no response (NR) | platelet count < 30 x 109 /l or less than 2-fold increase of baseline platelet count, confirmed on at least 2 separate occasions approximately 1 day apart, or bleeding | 28 days after first administration of the study drug | 
| Part (percent) of patients with loss of response (R) | platelet count below 30 x 109 /l or less than 2-fold increase of baseline platelet count or bleeding; platelet counts confirmed on at least 2 separate occasions approximately 1 day apart | 28 days after first administration of the study drug | 
| Part (percent) of patients with loss of complete response (CR) | platelet count below 100 x 109 /l or bleeding; platelet counts confirmed on at least 2 separate occasions approximately 1 day apart | 28 days after first administration of the study drug | 
| Time (in days) from treatment start to response (R) | Time calculated from first infusion (treatment start) to the day when the response (R) criteria are achieved | 28 days after first administration of the study drug | 
| Time (in days) from treatment to complete response (CR) | Time calculated from first infusion (treatment start) to the day when the complete response (CR) criteria are achieved | 28 days after first administration of the study drug | 
| Duration (in days) of response (R) | Time calculated from the day when the complete response (R) criteria are achieved, to the day when loss of complete response (R) criteria is achieved | 28 days after first administration of the study drug | 
| Duration (in days) of complete response (CR) | Time calculated from the day when the complete response (CR) criteria are achieved, to the day when loss of complete response (CR) criteria are achieved | 28 days after first administration of the study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVIG, ITP, immunomodulatory therapy, intravenous immunoglobulin, chronic primary immune thrombocytopenia