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

• ClinicalTrials.gov Identifier: NCT05422365
• Recruitment Status: Recruiting
• First Posted: June 16, 2022
• Last Update Posted: November 16, 2022
• Sponsor: Biopharma Plasma LLC
• Information provided by (Responsible Party): Biopharma Plasma LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Primary Immune Thrombocytopenia	Drug: Intravenous immunoglobulin (IVIG), 10% solution for infusion	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open, multicenter, international, uncontrolled
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: July 26, 2022
• Estimated Primary Completion Date: November 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

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 Name: Bioven, 10% solution for infusion

Outcome Measures

Primary Outcome Measures :

1. Part (percent) of patients with response (R) [ Time Frame: 28 days after first administration of the study drug ]
   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

Secondary Outcome Measures :

1. Part (percent) of patients with complete response (CR) [ Time Frame: 28 days after first administration of the study drug ]
   platelet count >100 x 109 /l, confirmed on at least 2 separate occasions at least 7 days apart, and absence of bleeding
2. Part (percent) of patients with no response (NR) [ Time Frame: 28 days after first administration of the study drug ]
   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
3. Part (percent) of patients with loss of response (R) [ Time Frame: 28 days after first administration of the study drug ]
   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
4. Part (percent) of patients with loss of complete response (CR) [ Time Frame: 28 days after first administration of the study drug ]
   platelet count below 100 x 109 /l or bleeding; platelet counts confirmed on at least 2 separate occasions approximately 1 day apart
5. Time (in days) from treatment start to response (R) [ Time Frame: 28 days after first administration of the study drug ]
   Time calculated from first infusion (treatment start) to the day when the response (R) criteria are achieved
6. Time (in days) from treatment to complete response (CR) [ Time Frame: 28 days after first administration of the study drug ]
   Time calculated from first infusion (treatment start) to the day when the complete response (CR) criteria are achieved
7. Duration (in days) of response (R) [ Time Frame: 28 days after first administration of the study drug ]
   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
8. Duration (in days) of complete response (CR) [ Time Frame: 28 days after first administration of the study drug ]
   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

Other Outcome Measures:

1. Frequency (percent) of adverse events [ Time Frame: 28 days after first administration of the study drug ]
   Part of the drug administration cases with adverse events, from all cases of study drug administration
2. Frequency of serious adverse events [ Time Frame: 28 days after first administration of the study drug ]
   Part of the drug administration cases with serious adverse events, from all cases of study drug administration

Eligibility Criteria

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

Criteria

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;

Contacts and Locations

Contacts

Contact: Yaroslav Zhebelenko, Ph.D., MD; +380977495979; y.zhebelenko@biopharma.ua

Contact: Iryna Stavna; i.stavna@biopharma.ua

Locations

Ukraine

Municipal non-profit enterprise "City Clinical Hospital No. 4" of the Dnipro City Council; Not yet recruiting

Dnipro, Ukraine, 49102

Contact: Anna Usenko

Sub-Investigator: Inna Sydorenko

Sub-Investigator: Iryna Selina

Principal Investigator: Anna Usenko

Municipal non-profit enterprise "Khmelnytskyi Regional Hospital" of the Khmelnytskyi Regional Council; Recruiting

Khmelnytskyi, Ukraine, 29010

Contact: Hryhorii Rekhtman

Sub-Investigator: Oleksandra Muzyka

Sub-Investigator: Zhanna Tkach

Principal Investigator: Hryhorii Rekhtman

Municipal Non-Profit Enterprise "Kirovohrad Regional Hospital of the Kirovohrad Regional Council"; Recruiting

Kropyvnytskyi, Ukraine, 25030

Contact: Iryna Yermolytska

Sub-Investigator: Olesia Kozachenko

Sub-Investigator: Olha Imanova

Medical Center "OK!Clinic+" of the Company with Limited Liability "International Institute of Clinical Research"; Recruiting

Kyiv, Ukraine, 02091

Contact: Olena Kyselova

Sub-Investigator: Mariia Mazur

Sub-Investigator: Olena Karpenko

Principal Investigator: Olena Kyselova

Municipal Non-Profit Enterprise of Kyiv Regional Council "Kyiv Regional Oncology Dispensary"; Not yet recruiting

Kyiv, Ukraine, 04107

Contact: Iryna Hartovska

Sub-Investigator: Hanna Drotsenko

Sub-Investigator: Olha Sviatenko

Principal Investigator: Iryna Hartovska

Municipal non-profit enterprise "Kyiv City Clinical Hospital No. 9" of the executive body of the Kyiv City Council (Kyiv City State Administration); Recruiting

Kyiv, Ukraine, 04112

Contact: Svitlana Sivkovych

Sub-Investigator: Viktoriia Starovoit

Principal Investigator: Svitlana Sivkovych

"Arensia Exploratory Medicine" Limited Liability Company Medical Center; Recruiting

Kyiv, Ukraine, 08112

Contact: Oksana Karnabeda

Sub-Investigator: Zoreslava Lysak

Sub-Investigator: Yuliia Mukhanova

Principal Investigator: Oksana Karnabeda

State Institution "Institute of Blood Pathology and Transfusion Medicine of the National Academy of Medical Sciences of Ukraine"; Recruiting

Lviv, Ukraine, 79044

Contact: Zvenyslava Masliak

Sub-Investigator: Tetiana Horodyska

Minicipal enterprise "Rivne regional clinical hospital" of Rivne regional council; Not yet recruiting

Rivne, Ukraine, 33007

Contact: Liudmyla Khokhliuk-Alekseichuk

Sub-Investigator: Nataliia Mizynets

Municipal Non-Profit Enterprise of Sumy Regional Council "Sumy Regional Clinical Hospital"; Not yet recruiting

Sumy, Ukraine, 40031

Contact: Iryna Dudchenko

Sub-Investigator: Pavlo Prydiuk

Municipal non-profit enterprise "Ternopil University Hospital" of Ternopil Regional Council; Recruiting

Ternopil, Ukraine, 46002

Contact: Renata Vybyrana

Sub-Investigator: Halyna Kmita

Sub-Investigator: Nadiia Khlebnikova

Municipal Non-Profit Enterprise "Zakarpattia Regional Clinical Hospital named after Andriy Novak" of Zakarpattia Regional Council; Recruiting

Uzhhorod, Ukraine, 88000

Contact: Yurii Popovych

Sub-Investigator: Olha Chundak

Sub-Investigator: Myroslava Popovych

Sponsors and Collaborators

Biopharma Plasma LLC

More Information

Additional Information:

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

• Responsible Party: Biopharma Plasma LLC
• ClinicalTrials.gov Identifier: NCT05422365
• Other Study ID Numbers: 2021-BV-ITP-BP
• First Posted: June 16, 2022
• Last Update Posted: November 16, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: After the scientific publication of trial results, 3 months later
• Access Criteria: For specialists in field medicine, pharmacy, scientists

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biopharma Plasma LLC:

IVIG; ITP; immunomodulatory therapy; intravenous immunoglobulin; chronic primary immune thrombocytopenia

Additional relevant MeSH terms:

Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations; Pharmaceutical Solutions; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin; Immunologic Factors; Physiological Effects of Drugs