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

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)

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.

Study Overview

• Status: Completed
• Conditions: Primary Immune Thrombocytopenia
• Intervention / Treatment: Drug: Intravenous immunoglobulin (IVIG), 10% solution for infusion

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 3

Contacts and Locations

Study Locations

• Ukraine
  • Dnipro, Ukraine, 49102
    • Municipal non-profit enterprise "City Clinical Hospital No. 4" of the Dnipro City Council
  • Khmelnytskyi, Ukraine, 29010
    • Municipal non-profit enterprise "Khmelnytskyi Regional Hospital" of the Khmelnytskyi Regional Council
  • Kropyvnytskyi, Ukraine, 25030
    • Municipal Non-Profit Enterprise "Kirovohrad Regional Hospital of the Kirovohrad Regional Council"
  • Kyiv, Ukraine, 02091
    • Medical Center "OK!Clinic+" of the Company with Limited Liability "International Institute of Clinical Research"
  • Kyiv, Ukraine, 04107
    • Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"
  • Kyiv, Ukraine, 04112
    • Municipal non-profit enterprise "Kyiv City Clinical Hospital No. 9" of the executive body of the Kyiv City Council (Kyiv City State Administration)
  • Kyiv, Ukraine, 08112
    • "Arensia Exploratory Medicine" Limited Liability Company Medical Center
  • Lviv, Ukraine, 79044
    • State Institution "Institute of Blood Pathology and Transfusion Medicine of the National Academy of Medical Sciences of Ukraine"
  • Rivne, Ukraine, 33007
    • Minicipal enterprise "Rivne regional clinical hospital" of Rivne regional council
  • Sumy, Ukraine, 40031
    • Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Hospital"
  • Ternopil, Ukraine, 46002
    • Municipal non-profit enterprise "Ternopil University Hospital" of Ternopil Regional Council
  • Uzhhorod, Ukraine, 88000
    • Municipal Non-Profit Enterprise "Zakarpattia Regional Clinical Hospital named after Andriy Novak" of Zakarpattia Regional Council

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Main Group; 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; 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.; Other Names: Bioven, 10% solution for infusion

What is the study measuring?

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. Complete response (CR) was achieved in 13 patients during the study. CR = 13/32 = 40.63 % (23,61%; 57,64%) This corresponds 40,63% from total number of patients. The confidence interval for this value is 23.61% to 57.64%	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 a 2-fold increase of the baseline count. It should be confirmed by at least 2 blood tests or presence of bleeding	28 days after first administration of the study drug
Part (Percent) of Patients With Loss of Response (R)	Decreasing platelet count (< 30 x 109/L or less than a 2-fold increase of the baseline count) or development of bleeding. Platelet count should be confirmed at least two times, with an interval of 1 day.	28 days after first administration of the study drug
Part (Percent) of Patients With Loss of Complete Response (CR)	decreased platelet count <100 x 109/L or development of bleeding	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency (Percent) of Adverse Events	Part of the drug administration cases with adverse events, from all cases of study drug administration	28 days after first administration of the study drug
Frequency of Serious Adverse Events	Part of the drug administration cases with serious adverse events, from all cases of study drug administration	28 days after first administration of the study drug

Collaborators and Investigators

• Sponsor: Biopharma Plasma LLC

Publications and helpful links

Helpful Links

• Guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg), rev. 4, 16 December 2021

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2022
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: IVIG; ITP; intravenous immunoglobulin; immunomodulatory therapy; chronic primary immune thrombocytopenia
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Pharmaceutical Solutions; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 2021-BV-ITP-BP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The results will be published after trial completion. Access to parts of the Clinical Study Report (CSR) planned after the release of scientific publications.

Individual participant data (IPD) with the code of each patient will be available In CSR

• IPD Sharing Time Frame: After the scientific publication of trial results, 3 months later
• IPD Sharing Access Criteria: For specialists in field medicine, pharmacy, scientists
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No