This Clinical Study is to Test Efficacy and Safety of BT595 in Chronic Primary Immune Thrombocytopenia (ITP)

Study Overview
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Brief Summary
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The main purpose of this study is to assess the efficacy and safety of BT595 in adult subjects with chronic ITP. The primary objective of this study is to determine the rate of subjects with a response. A response is defined as a platelet count of ≥30×10^9/L and at least a 2 fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding. The secondary objectives of this study, in addition to further efficacy assessments, are to evaluate the safety of BT595.

Official Title
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An Open Label, Prospective, Randomized, Multicenter Study Investigating Clinical Efficacy and Safety of the Human Normal Immunoglobulin for Intravenous Administration BT595 in Patients With Chronic Primary Immune Thrombocytopenia (ITP)

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Biological: BT595


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Diagnosis of chronic ITP (>12 months' duration), including diagnosis of refractory ITP, and as defined by the International Working Group (Rodeghiero et al, 2009), where ITP is described as an autoimmune disorder characterized by isolated thrombocytopenia in the absence of other causes or disorders that may be associated with thrombocytopenia Treatment is indicated because of a high risk of bleeding or a need to raise the platelet count Mean screening platelet count of <30×10^9/L from 3 qualifying platelet counts performed within approximately 7 to 14 days before the start of treatment, with no individual platelet count above 35×10^9/L. The subject may be rescreened if the mean screening platelet count is ≥30×10^9/L. (Note: If a subject is rescreened, all screening laboratory tests must be repeated.) Main Exclusion Criteria: Secondary thrombocytopenia or acquired medical conditions known to be associated with secondary thrombocytopenia, such as chronic lymphocytic leukemia; lymphoma; multiple myeloma; thyroid disease; or other forms of thrombocytopenia, such as drug induced thrombocytopenia; cirrhotic liver diseases; antiphospholipid syndrome; environmental thrombocytopenia; and bone marrow diseases Severe concomitant diseases that in the judgment of the investigator will interfere with the study, such as autoimmune hemolytic anemia, acute renal failure, and noncontrolled arterial hypertension Laboratory findings (e.g., abnormal laboratory values for hemoglobin, transaminase levels [alanine aminotransferase, aspartate aminotransferase], total bilirubin, creatinine, blood urea nitrogen, and immunoglobulins G, A, M) that preclude participation Positive Coombs test (direct and indirect) Planned invasive procedures during the time frame of the study Maintenance therapy with intravenous immunoglobulins (IVIgs) or infusion of IVIgs within 3 months before start of the study Unresponsive to previous IVIg treatment Additional therapy with high dose corticosteroids (equivalent to >30 mg prednisone/day), thrombopoietin receptor agonists, and/or immunosuppressives and/or other therapies (e.g., infusion of platelets) within 1 month before the start of the study (Note: Subjects on stable doses of ITP active treatment must not have modified the dose in the preceding 2 weeks and must maintain their prestudy dose during the study. Corticosteroids should not be given as a premedication. Rescue therapy with short courses [i.e., 1 to 4 days] of high dose steroids and IVIgs are allowed up to 2 weeks before study inclusion.) History of thrombotic events (including myocardial infarction, cerebral vascular accident [including stroke], pulmonary embolism, and deep vein thrombosis) 6 months before treatment start with BT595 or the presence of significant risk factors for thrombotic events Therapy with live attenuated virus vaccines 3 months before start of the study Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 day treatment schedule<br>Patients will receive a dosage of 1 g/kg bw per day of BT595 for 2 consecutive days | Biological: BT595<br> <br> * Other names: Human Immunoglobulin;|
| Experimental: 5 day treatment schedule<br>Patients will receive a dosage of 0.4 g/kg bw per day of BT595 for 5 consecutive days | Biological: BT595<br> <br> * Other names: Human Immunoglobulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects with response (R) | The rate of subjects with response is defined as subjects with a platelet count of ≥30×10^9/L and at least a 2 fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects with complete response (CR) | The number of subjects with CR, which is defined as a platelet count ≥100×10^9/L, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding | 1 month | 
| The percentage of subjects with complete response (CR) | The percentage of subjects with CR, which is defined as a platelet count ≥100×10^9/L, confirmed on at least 2 separate occasions at least 7 days apart, and the absence of bleeding | 1 month | 
| The number of subjects with no response (NR) | The number of subjects with NR, which is defined as subjects without R, i.e. a platelet count <30×10^9/L or less than a 2 fold increase of baseline platelet count, confirmed on at least 2 separate occasions, approximately 1 day apart, or bleeding | 1 month | 
| The percentage of subjects with no response (NR) | The percentage of subjects with NR, which is defined as subjects without R, i.e. a platelet count <30×10^9/L or less than a 2 fold increase of baseline platelet count, confirmed on at least 2 separate occasions, approximately 1 day apart, or bleeding | 1 month | 
| The number of subjects with a loss of response | The number of subjects with a loss of response (only in subjects who previously had CR or R), which is defined as a platelet count <100×10^9/L or bleeding (from CR) or platelet count <30×10^9/L or less than 2 fold increase of the baseline platelet count, or bleeding (from R). Platelet counts will be confirmed on at least 2 separate occasions approximately 1 day apart | 1 month | 
| The percentage of subjects with a loss of response | The percentage of subjects with a loss of response (only in subjects who previously had CR or R), which is defined as a platelet count <100×10^9/L or bleeding (from CR) or platelet count <30×10^9/L or less than 2 fold increase of the baseline platelet count, or bleeding (from R). Platelet counts will be confirmed on at least 2 separate occasions approximately 1 day apart | 1 month | 
| Time to Response (R) | Time to response (R), which is defined as the time from the start of treatment to the time of achievement of CR or R | 1 month | 
| Duration of response (R), | Duration of response (R), which is defined as the time from the achievement of CR or R to loss of CR or R | 1 month | 
| The number of subjects with response to ≥50×10^9/L | The number of subjects with response to ≥50×10^9/L, which is defined as a platelet count increase to at least ≥50×10^9/L within 7 days of the first BT595 infusion | 1 month | 
| The percentage of subjects with response to ≥50×10^9/L | The percentage of subjects with response to ≥50×10^9/L, which is defined as a platelet count increase to at least ≥50×10^9/L within 7 days of the first BT595 infusion | 1 month | 
| Subject's maximum platelet count achieved |  | 1 month | 
| Time to subject's maximum platelet count |  | 1 month | 
| Time course of platelet count |  | 1 month | 
| Occurrence of bleeding symptoms |  | 1 month |