Purpura, Thrombocytopenic, Idiopathic
Conditions
Keywords
Idiopathic (Immune) Thrombocytopenic Purpura, Immunoglobulin G
Brief summary
The objective of this study is to determine if the safety and tolerability of Immune Globulin Intravenous (Human), 10% Caprylate/Chromatograph Purified (IGIV-C) is similar when infused at two different infusion rates.
Detailed description
This is a prospective, randomized, single-center, open, cross-over trial in patients with a confirmed diagnosis of Idiopathic Thrombocytopenia Purpura (ITP). ITP is defined as isolated thrombocytopenia in a patient with no other clinically apparent associated conditions or factors that are known to cause thrombocytopenia as defined by the ITP Practice Guidelines Committee of the American Society of Hematology. Immune Globulin Intravenous (Human), 10% Caprylate/Chromatography Purified (IGIV-C) at a dose of 1.0 g/kg will be given on 2 occasions as a single daily infusion for platelet counts \< 30,000 microliters (uL) or if clinically indicated, at maximum intervals of six weeks. Eligible patients will be randomized into one of two cross-over groups. Patients randomized to Group 1 will receive their first IGIV-C infusion at a rate of 0.08 mL/kg/min and their second infusion at a rate of 0.14 mL/kg/min. Conversely patients randomized to Group 2 will receive their first IGIV-C infusion at a rate of 0.14 mL/kg/min and their second infusion at a rate of 0.08 mL/kg/min according to the following schema: Group 1: * Infusion #1 (Week 0) IGIV-C (0.08 mL/kg/min) * Infusion #2 (Week \<6) IGIV-C (0.14 mL/kg/min) Group 2: * Infusion #1 (Week 0) IGIV-C (0.14 mL/kg/min) * Infusion #2 (Week \<6) IGIV-C (0.08 mL/kg/min)
Interventions
IGIV-C 10% at a dose of 1.0g/kg was to be given on 2 occasions as a single daily infusion: Group 1 were to receive their first IGIV-C, 10-% infusion at a rate of 0.08 mL/kg/min and a second infusion at 0.14 mL/kg/min. and Group 2 were to receive their first IGIV-C, 10-% infusion at a rate of 0.14 mL/kg/min and a second infusion at a rate of 0.08 mL/kg/min.
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent from patient or legal guardian (according to institutional review board requirements)obtained prior to initiation of any study related procedures * Male and female subjects age between 12 and 75 years * Confirmed diagnosis of ITP logged in medical records available prior to entry into the trial. * Patients must have a platelet count \< 30 x Giga/L (this level can be higher if clinically indicated). * Previously splenectomized patients may be included. * Any previously conducted bone marrow aspirations if conducted following diagnosis of ITP must be consistent with the ITP diagnosis (increased or normal levels of megakaryocytes in otherwise normal bone marrow).
Exclusion criteria
* History of allergic or other clinically significant reaction to human gamma globulin or other plasma proteins and/or blood products. * Female patient who is pregnant or lactating or is not on an adequate program of contraception if of child-bearing potential. * Documented history of selective immunoglobulin A (IgA) deficiency (serum \<5.0 mg/dL) and known antibodies to IgA. * Currently on intermittent prednisone therapy. Prednisone therapy is allowed only if the patient has been on stable daily doses of prednisone for the preceding month and maintains the same treatment regimen throughout the study. * Renal or liver impairment defined by creatinine \> 2.5 mg/dL, or direct bilirubin \>1.5 X the upper limit of normal or liver transaminases (AST or ALT) \> 3 times the upper limit of normal. * Received anti-D or IGIV infusions within the past 14 days * Pre-treatment with the exception of acetominophen, routinely required to control/ameliorate IGIV infusion-related adverse events (AEs), or any patient who has been, unresponsive to IGIV therapy for their ITP * History or clinical evidence of medical conditions felt to be the underlying cause of their thrombocytopenia. Such conditions commonly include systemic lupus erythematosus, history of chronic lymphocytic leukemia, dysplasia, agammaglobulinemia, treatment with heparin, quinidine, quinine, trimethoprim-sulfamethoxazole, or ticlopidine or any other drug thought to be the cause of patient's thrombocytopenia, congenital or hereditary thrombocytopenia, or pseudothrombocytopenia (clumping on peripheral blood smear) * Conditions that could alter protein catabolism and/or immunoglobulin G (IgG) utilization (e.g. protein-losing enteropathies, nephrotic syndrome) * Congestive heart failure (New York Heart Association Stage III or IV) * Diabetes mellitus * Paraproteinemia * Concomitant nephrotoxic drugs * Hemoglobin level more than 2g/L below the lower limit of normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Free Hemoglobin | 24 hours after treatment | Free hemoglobin as a measure to assess hemolysis. |
| Hematocrit | 24 hrs after treatment | Hematocrit as a measure to assess hemolysis |
| Red Blood Cells | 24 hrs after treatment | Red blood cells as a measure to assess hemolysis |
| Change From Baseline in Platelet Levels | 24 hours Post infusion and Day 7 | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Subjects With Infusion Related Adverse Events | 48 hours after treatment |
Countries
United States
Participant flow
Recruitment details
Single-center, open label study in patients with a confirmed diagnosis of Idiopathic Thrombocytopenic Purpura (ITP).
Participants by arm
| Arm | Count |
|---|---|
| IGIV-C, 10% - 0.08/0.14 mL/kg/Min Infusion #1 (Week 0 IGIV-C (0.08 mL/kg/min); Infusion #2 (Week \<6) IGIV-C (0.14 mL/kg/min) | 4 |
| IGIV-C, 10% - 0.14/0.08 mL/kg/Min Infusion #1 (Week 0) IGIV-C (0.14 mL/kg/min); Infusion #2 (Week \<6) IGIV-C (0.08 mL/kg/min) | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Infusion (Week <6) | Pt did not meet study requirement | 1 | 0 |
Baseline characteristics
| Characteristic | IGIV-C, 10% - 0.14/0.08 mL/kg/Min | IGIV-C, 10% - 0.08/0.14 mL/kg/Min | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 47.50 years STANDARD_DEVIATION 14.89 | 47.75 years STANDARD_DEVIATION 15.78 | 47.63 years STANDARD_DEVIATION 14.2 |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 7 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 |
Outcome results
Primary
Change From Baseline in Platelet Levels
Time frame: 24 hours Post infusion and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IGIV-C, 10% (0.08 mL/kg/Min) | Change From Baseline in Platelet Levels | Baseline | 29.50 Giga/L | Standard Deviation 28.47 |
| IGIV-C, 10% (0.08 mL/kg/Min) | Change From Baseline in Platelet Levels | 24 hours post infusion | 21.17 Giga/L | Standard Deviation 35.49 |
| IGIV-C, 10% (0.08 mL/kg/Min) | Change From Baseline in Platelet Levels | Day 7 | 76 Giga/L | Standard Deviation 138.35 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Change From Baseline in Platelet Levels | Baseline | 6.86 Giga/L | Standard Deviation 3.39 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Change From Baseline in Platelet Levels | 24 hours post infusion | 42.29 Giga/L | Standard Deviation 12.41 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Change From Baseline in Platelet Levels | Day 7 | 118.7 Giga/L | Standard Deviation 165.8 |
Primary
Free Hemoglobin
Free hemoglobin as a measure to assess hemolysis.
Time frame: 24 hours after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGIV-C, 10% (0.08 mL/kg/Min) | Free Hemoglobin | 13.057 g/dL | Standard Deviation 1.778 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Free Hemoglobin | 12.371 g/dL | Standard Deviation 2.644 |
Primary
Hematocrit
Hematocrit as a measure to assess hemolysis
Time frame: 24 hrs after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGIV-C, 10% (0.08 mL/kg/Min) | Hematocrit | 36.80 percentage of blood | Standard Deviation 4.711 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Hematocrit | 35.043 percentage of blood | Standard Deviation 6.793 |
Primary
Red Blood Cells
Red blood cells as a measure to assess hemolysis
Time frame: 24 hrs after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IGIV-C, 10% (0.08 mL/kg/Min) | Red Blood Cells | 4.1514 10^12 cells/L | Standard Deviation 0.482 |
| IGIV-C, 10% (0.14 mL/kg/Min) | Red Blood Cells | 4.0786 10^12 cells/L | Standard Deviation 0.8258 |
Secondary
Number of Subjects With Infusion Related Adverse Events
Time frame: 48 hours after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IGIV-C, 10% (0.08 mL/kg/Min) | Number of Subjects With Infusion Related Adverse Events | 2 participants |
| IGIV-C, 10% (0.14 mL/kg/Min) | Number of Subjects With Infusion Related Adverse Events | 3 participants |