Primary Thrombocytopenia
Conditions
Keywords
ITP, Primary immune thrombocytopenia
Brief summary
NewGam is a newly developed human normal immunoglobulin solution for intravenous administration (IGIV). This study will evaluate the safety and efficacy of NewGam 10% in patients with primary immune thrombocytopenia.
Detailed description
The primary objective of the study is to assess the efficacy of NewGam in correcting the platelet count. The secondary objective of the study is to evaluate the safety of NewGam. Safety will be assessed by monitoring vital signs, physical examination, evaluation of adverse events (AE) and laboratory parameters, and viral safety testing.
Interventions
DRUGNewGam
NewGam is a solution of human normal immunoglobulin 10% treated with solvent/detergent and nanofiltered for intravenous administration.
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age of ≥ 18 and ≤ 65 years. 2. Confirmed diagnosis of chronic primary immune thrombocytopenia (ITP) (diagnosed with a threshold platelet count \< 100x10\^9/L) of at least 12 months duration. 3. Platelet count of no more than 20x10\^9/L with or without bleeding manifestations. 4. Freely given written informed consent from patient. 5. Women of childbearing potential must have a negative result on a pregnancy test (human chorionic gonadotropin \[HCG\]-based assay) and need to practice contraception using a method of proven reliability for the duration of the study.
Exclusion criteria
1. Thrombocytopenia secondary to other diseases (such as acquired immunodeficiency syndrome \[AIDS\] or systemic lupus erythematosus \[SLE\]), or drug-related thrombocytopenia. 2. Administration of intravenous immunoglobulin (IGIV), anti-D immunoglobulin or thrombopoietin receptor agonists, or other platelet enhancing drugs (including immunosuppressive or other immunomodulatory drugs) within 3 weeks before enrollment, except for: * Long-term corticosteroid therapy when the dose has been stable during the preceding 3 weeks and no dosage change is planned until study Day 22. * Long-term azathioprine, cyclophosphamide, or attenuated androgen therapy when the dose has been stable during the preceding 3 months and no dosage change is planned until study Day 22. 3. Unresponsive to previous treatment with IGIV or anti-D immunoglobulin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders | Day 1 to Day 8 | A responder is a study participant with an increase in platelets to ≥ 50x10\^9/L within 7 days after the first infusion, ie, by study Day 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Alternative Responders | Day 1 to Day 22 | An alternative responder is a study participant with an increase in platelets to ≥ 30x10\^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding. |
| Percentage of Complete Responders | Day 1 to Day 22 | A complete responder is a study participant with an increase in platelets to ≥ 100x10\^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding. |
| Percentage of Alternative Responders Who Lost the Response | Day 1 to Day 22 | An alternative responder who lost the response is a study participant who met the criterion for an alternative response but who then deteriorated, ie, their platelet count decreased to \< 30x10\^9/L, their platelet count decreased to less than double the baseline count, or bleeding occurred. |
| Percentage of Complete Responders Who Lost the Response | Day 1 to Day 22 | A complete responder who lost the response is a study participant who met the criterion for a complete response but who then deteriorated, ie, their platelet count decreased to \< 100x10\^9/L or bleeding occurred. |
| Time to a Response | Day 1 to Day 8 | A study participant had a response if their platelets increased to ≥ 50x10\^9/L within 7 days after the first infusion, ie, by study Day 8. |
| Time to an Alternative Response | Day 1 to Day 22 | A study participant had a response if their platelets increased to ≥ 30x10\^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding. |
| Time to a Complete Response | Day 1 to Day 22 | A study participant had a complete response if their platelets increased to ≥ 100x10\^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding. |
| Maximum Platelet Count | Day 1 to Day 22 | The maximum platelet count achieved during the study is presented. |
| Duration of an Alternative Response | Day 1 to Day 22 | The duration of an alternative response was defined as the time from when an alternative response was achieved until the platelet count fell below 50x10\^9/L. |
| Duration of a Complete Response | Day 1 to Day 22 | The duration of a complete response was defined as the time from when a complete response was achieved until the platelet count fell below 50x10\^9/L. |
| Platelet Count by Visit | Day 1 to Day 22 | The platelet count at each study visit are presented. |
| Percentage of Responders Who Achieved a Normal Platelet Count | Day 1 to Day 22 | The percentage of responders who achieved a normal platelet count is presented. |
| Bleeding Intensity | Day 1 to Day 22 | The percentage of participants with various intensities of overall bleeding, epistaxis (bleeding of the nose), oral bleeding, and skin bleeding graded as none, minor, mild, moderate, or severe at Baseline and Day 22 are reported. |
| Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L | Day 1 to Day 2 | The percentage of participants who achieved a platelet count \> 30x10\^9/L within 1 and 2 days after infusion is reported. |
| Duration of a Response | Day 1 to Day 22 | The duration of a response was defined as the time from when a response was achieved until the platelet count fell below 50x10\^9/L. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NewGam Each participant received 1 g/kg NewGam intravenously on 2 consecutive days. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Investigator Judgement | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Patient | 2 |
Baseline characteristics
| Characteristic | NewGam |
|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 15.34 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 40 |
| serious Total, serious adverse events | 6 / 40 |
Outcome results
Primary
Percentage of Responders
A responder is a study participant with an increase in platelets to ≥ 50x10\^9/L within 7 days after the first infusion, ie, by study Day 8.
Time frame: Day 1 to Day 8
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Responders | 80.6 Percentage of participants |
Secondary
Bleeding Intensity
The percentage of participants with various intensities of overall bleeding, epistaxis (bleeding of the nose), oral bleeding, and skin bleeding graded as none, minor, mild, moderate, or severe at Baseline and Day 22 are reported.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NewGam | Bleeding Intensity | Overall - Total - Baseline | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Total - Day 8 | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Total - Day 22 | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Mild - Baseline | 5.6 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Mild - Day 8 | 2.9 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Mild - Day 22 | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Moderate - Day 8 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Moderate - Day 22 | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Severe - Baseline | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Severe - Day 8 | 0 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - None - Baseline | 83.3 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - None - Day 22 | 91.7 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Minor - Baseline | 8.3 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Moderate - Baseline | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Moderate - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Severe - Baseline | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Severe - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Total - Baseline | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Total - Day 22 | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Severe - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Severe - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - None - Baseline | 36.1 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - None - Day 8 | 91.2 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - None - Day 22 | 72.2 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Minor - Baseline | 38.9 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Total - Baseline | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Minor - Day 8 | 5.9 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Minor - Day 22 | 19.4 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Moderate - Baseline | 19.4 Percentage of participants |
| NewGam | Bleeding Intensity | Overall - Severe - Day 22 | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Total - Baseline | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Total - Day 22 | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Minor - Day 22 | 8.3 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Mild - Baseline | 5.6 Percentage of participants |
| NewGam | Bleeding Intensity | Epistaxis - Mild - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - None - Baseline | 75.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - None - Day 22 | 86.1 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Minor - Baseline | 13.9 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Minor - Day 22 | 8.3 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Mild - Baseline | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Mild - Day 22 | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Moderate - Baseline | 5.6 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Moderate - Day 22 | 2.8 Percentage of participants |
| NewGam | Bleeding Intensity | Oral bleeding - Severe - Baseline | 5.6 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Total - Day 22 | 100.0 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - None - Baseline | 41.7 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - None - Day 22 | 77.8 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Minor - Baseline | 25.0 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Minor - Day 22 | 22.2 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Mild - Baseline | 27.8 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Mild - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Moderate - Baseline | 5.6 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Moderate - Day 22 | 0.0 Percentage of participants |
| NewGam | Bleeding Intensity | Skin bleeding - Severe - Baseline | 0.0 Percentage of participants |
Secondary
Duration of a Complete Response
The duration of a complete response was defined as the time from when a complete response was achieved until the platelet count fell below 50x10\^9/L.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Duration of a Complete Response | 12.5 Days |
Secondary
Duration of an Alternative Response
The duration of an alternative response was defined as the time from when an alternative response was achieved until the platelet count fell below 50x10\^9/L.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Duration of an Alternative Response | 18.5 Days |
Secondary
Duration of a Response
The duration of a response was defined as the time from when a response was achieved until the platelet count fell below 50x10\^9/L.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Duration of a Response | 14.0 Days |
Secondary
Maximum Platelet Count
The maximum platelet count achieved during the study is presented.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NewGam | Maximum Platelet Count | 236.9 10^9 platelets/L | Standard Deviation 205.18 |
Secondary
Percentage of Alternative Responders
An alternative responder is a study participant with an increase in platelets to ≥ 30x10\^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Alternative Responders | 66.7 Percentage of participants |
Secondary
Percentage of Alternative Responders Who Lost the Response
An alternative responder who lost the response is a study participant who met the criterion for an alternative response but who then deteriorated, ie, their platelet count decreased to \< 30x10\^9/L, their platelet count decreased to less than double the baseline count, or bleeding occurred.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Alternative Responders Who Lost the Response | 45.8 Percentage of participants |
Secondary
Percentage of Complete Responders
A complete responder is a study participant with an increase in platelets to ≥ 100x10\^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Complete Responders | 50.0 Percentage of participants |
Secondary
Percentage of Complete Responders Who Lost the Response
A complete responder who lost the response is a study participant who met the criterion for a complete response but who then deteriorated, ie, their platelet count decreased to \< 100x10\^9/L or bleeding occurred.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Complete Responders Who Lost the Response | 77.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L
The percentage of participants who achieved a platelet count \> 30x10\^9/L within 1 and 2 days after infusion is reported.
Time frame: Day 1 to Day 2
Population: Safety set: All participants enrolled in the study who received at least part of 1 dose of NewGam.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NewGam | Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L | Day 1 | 55.0 Percentage of participants |
| NewGam | Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L | Day 2 | 77.5 Percentage of participants |
Secondary
Percentage of Responders Who Achieved a Normal Platelet Count
The percentage of responders who achieved a normal platelet count is presented.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NewGam | Percentage of Responders Who Achieved a Normal Platelet Count | 79.3 Percentage of participants |
Secondary
Platelet Count by Visit
The platelet count at each study visit are presented.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NewGam | Platelet Count by Visit | Baseline | 8.8 10^9 platelets/L | Standard Deviation 5.76 |
| NewGam | Platelet Count by Visit | Day 3 | 115.0 10^9 platelets/L | Standard Deviation 85.58 |
| NewGam | Platelet Count by Visit | Day 4 | 154.6 10^9 platelets/L | Standard Deviation 118.04 |
| NewGam | Platelet Count by Visit | Day 5 | 168.2 10^9 platelets/L | Standard Deviation 149.89 |
| NewGam | Platelet Count by Visit | Day 6 | 179.3 10^9 platelets/L | Standard Deviation 178.64 |
| NewGam | Platelet Count by Visit | Day 7 | 206.3 10^9 platelets/L | Standard Deviation 195.75 |
| NewGam | Platelet Count by Visit | Day 8 | 186.5 10^9 platelets/L | Standard Deviation 205.44 |
| NewGam | Platelet Count by Visit | Day 2 | 41.6 10^9 platelets/L | Standard Deviation 31.41 |
| NewGam | Platelet Count by Visit | Day 15 | 88.1 10^9 platelets/L | Standard Deviation 130.07 |
| NewGam | Platelet Count by Visit | Day 22/End of treatment | 41.4 10^9 platelets/L | Standard Deviation 65.48 |
Secondary
Time to a Complete Response
A study participant had a complete response if their platelets increased to ≥ 100x10\^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Time to a Complete Response | 2.0 Days |
Secondary
Time to an Alternative Response
A study participant had a response if their platelets increased to ≥ 30x10\^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time frame: Day 1 to Day 22
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Time to an Alternative Response | 1.0 Days |
Secondary
Time to a Response
A study participant had a response if their platelets increased to ≥ 50x10\^9/L within 7 days after the first infusion, ie, by study Day 8.
Time frame: Day 1 to Day 8
Population: Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NewGam | Time to a Response | 2.0 Days |