Chronic Idiopathic Thrombocytopenic Purpura
Conditions
Keywords
Idiopathic Thrombocytopenic Purpura, Bleeding disorders, Immune System and Disorders
Brief summary
To determine if GAMMAPLEX raises the platelet count of subjects with chronic ITP to a threshold of 50 x 109/L, similar to that of published response \>60%. Also to assess the safety of GAMMAPLEX and determine if platelet counts are maintained at 50 x 109/L in subjects with chronic ITP for.
Detailed description
The primary objective is to determine if BPL's GAMMAPLEX raises the platelet count of subjects with chronic ITP to a threshold of 50 x 109/L, similar to that of published response \>60%. The secondary objectives are: 1) to determine the safety of GAMMAPLEX at the dosage used in this study. 2) to determine if GAMMAPLEX maintains platelet counts of ³ 50 x 109/L in subjects with chronic ITP for a period of time similar to that of a published data.
Interventions
BIOLOGICALGammaplex, intravenous immunoglobulin
Dosage form: Gammaplex® is a sterile liquid of 5 % w/v normal immunoglobulin. Gammaplex® contains 5 g/100 mL of human normal immunoglobulin (i.e. 50 g/L, of which virtually 100% is IgG). The first course of GAMMAPLEX will be administered as an intravenous infusion of 1 g/kg on each of 2 consecutive days. If required, a further 1 or 2 courses on the same dosage regimen may be administered in the period Day 32 to Day 90 following the first course of GAMMAPLEX.
Sponsors
Bio Products Laboratory
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females aged between 18 and 70 years. 2. Confirmed diagnosis of chronic ITP of at least 6 months duration. 3. Platelet count of less than or equal to 20 x 10 9/L at enrollment. 4. Absence of other conditions that, in the opinion of the investigator, could cause thrombocytopenia. 5. If subjects were treated with corticosteroids the treatment regimen/dose must have been stable (for a minimum of 2 weeks before screening). The dose of corticosteriod or other immunosuppressant should have remained constant until Day 32. 6) If subjects were being treated with cyclophosphamide, azathioprine or attenuated androgens, the treatment regimen and dose must have been stable for a minimum of 2 months before Day 1. The dose of corticosteriod or other immunosuppressant should have remained constant until Day 32. 7) Splenectomized subjects and both Rh(D)+ and Rh(D)- subjects may be included. 8\) The subject has signed an informed consent form (subjects must be at least 18 years old), and/or the subject's legal guardian has signed the informed consent form if indicated 9) If a subject is a female of child-bearing potential, she must have a negative result on a urine-based HCG pregnancy test. 10\) If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.
Exclusion criteria
1. A history of any severe or anaphylactic reaction to blood or any blood-derived product, or any severe reaction to IGIV or any other IgG preparation. 2. Intolerance to any component of the investigational product. 3. Received any live virus vaccine within the last 3 months prior to Day1. 4. Received an IGIV preparation within 1 month prior to Day 1. 5. Were currently receiving, or has received, any investigational agent within the 1 month prior to Day 1. 6. Received any blood, blood product, or blood derivative within the 1 month prior to Day 1. 7. Received Rituximab within the 3 months before Day 1. 8. Pregnant or nursing. 9. Tested positive for any of the following at screening: HBsAg, NAT for HCV, NAT for HIV, Antibodies to HCV or HIV 1 or 2. 10. Had levels greater than 2.5 times the upper limit of normal at screening, as defined by the central laboratory, of alanine aminotransferase or aspartate aminotransferase. 11. Had severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or BUN greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); on dialysis; a history of acute renal failure. 12. Known to have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months. 13. History of deep vein thrombosis (DVT) or thrombotic complications of IGIV therapy. 14. Any history or sign of hyperviscosity, transient ischemic attack (TIA), stroke, other thromboembolic event, or unstable angina. 15. Suffered from any acute or chronic medical conditions (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing enteropathy) that, in the opinion of the investigator, may interfere with the conduct of the study. 16. An acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (defined as an absolute neutrophil count (ANC) \< 1 x 109/L). 17. Non-controlled arterial hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>90 mmHg). 18. Anemic (hemoglobin \<10 g/dL) at screening. 19. Unlikely to adhere to the protocol requirements of the study or is likely to be uncooperative.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects With Chronic ITP Treated With Gammaplex Whose Platelet Count Reached a Threshold of 50 x 10^9/L. | 9 days | The number of subjects with chronic ITP treated following treatment with Gammaplex who attained a platelet count of ≥ 50 x 10\^9/L by Day 9. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Safety of GAMMAPLEX at the Dosage Used in This Study. | AEs were documented from the date the informed consent form was signed until the End of Study visit on Day 90. | The safety variables used to assess safety were the following: * Adverse events * The number and percent of infusions with at least 1 adverse event(AE) that occurs during an infusion or within 72 hours after the infusion stops * Nature, severity, and frequency of AEs * Suspected unexpected serious adverse reactions (SUSARs) * Vital signs * Clinical laboratory tests and Direct Coombs' Test * Transmission of viruses * Physical examination |
| Duration of Time That the Platelet Count of Subjects With Chronic ITP Treated With Gammaplex Remained ≥ 50 x 10^9/L. | Days 1, 2, 3, 5, 9, 14, 21, 32. | Blood samples were collected to measure platelet counts and the duration of time for which the platelet count remained ≥50 x 10\^9/L was measured. |
Countries
Argentina, India, United States
Participant flow
Recruitment details
First enrollment: 04 September 2007. Last Subject completed: 05 August 2011. Thirty-five sites in the United States, India and Argentina, all hospital clinics.
Pre-assignment details
This was an open label study. All enrolled subjects received study medication.
Participants by arm
| Arm | Count |
|---|---|
| GAMMAPLEX The first course of GAMMAPLEX was administered as an intravenous infusion of 1g/kg on each of 2 consecutive days. If required, a further 1 or 2 courses on the same dosage regimen was administered in the period Day 32 to Day 90 following the first course of GAMMAPLEX. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Required other therapeutic intervention | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GAMMAPLEX |
|---|---|
| Age, Categorical <=18 years | 3 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age Continuous | 36 years STANDARD_DEVIATION 18 |
| Region of Enrollment Argentina | 5 participants |
| Region of Enrollment India | 21 participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 35 |
| serious Total, serious adverse events | 4 / 35 |
Outcome results
Primary
The Number of Subjects With Chronic ITP Treated With Gammaplex Whose Platelet Count Reached a Threshold of 50 x 10^9/L.
The number of subjects with chronic ITP treated following treatment with Gammaplex who attained a platelet count of ≥ 50 x 10\^9/L by Day 9.
Time frame: 9 days
Population: Any subject who started treatment with GAMMAPLEX and whose central laboratory results taken prior to infusion on Day 1 were within specified protocol parameters, was included in the intent-to-treat (ITT) population for analysis of efficacy and safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMMAPLEX | The Number of Subjects With Chronic ITP Treated With Gammaplex Whose Platelet Count Reached a Threshold of 50 x 10^9/L. | 29 participants |
Secondary
Duration of Time That the Platelet Count of Subjects With Chronic ITP Treated With Gammaplex Remained ≥ 50 x 10^9/L.
Blood samples were collected to measure platelet counts and the duration of time for which the platelet count remained ≥50 x 10\^9/L was measured.
Time frame: Days 1, 2, 3, 5, 9, 14, 21, 32.
Population: Any subject who started treatment with GAMMAPLEX and whose central laboratory results taken prior to infusion on Day 1 were within specified protocol parameters, was included in the intent-to-treat (ITT) population for analysis of efficacy and safety.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GAMMAPLEX | Duration of Time That the Platelet Count of Subjects With Chronic ITP Treated With Gammaplex Remained ≥ 50 x 10^9/L. | 10 days |
Secondary
The Safety of GAMMAPLEX at the Dosage Used in This Study.
The safety variables used to assess safety were the following: * Adverse events * The number and percent of infusions with at least 1 adverse event(AE) that occurs during an infusion or within 72 hours after the infusion stops * Nature, severity, and frequency of AEs * Suspected unexpected serious adverse reactions (SUSARs) * Vital signs * Clinical laboratory tests and Direct Coombs' Test * Transmission of viruses * Physical examination
Time frame: AEs were documented from the date the informed consent form was signed until the End of Study visit on Day 90.
Population: Any subject who started treatment with GAMMAPLEX and whose central laboratory results taken prior to infusion on Day 1 were within specified protocol parameters, was included in the intent-to-treat (ITT) population for analysis of efficacy and safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GAMMAPLEX | The Safety of GAMMAPLEX at the Dosage Used in This Study. | 8.6 % of subjects with product related SAEs |