Thrombocytopenia in Pediatric Subjects With Immune Idiopathic Thrombocytopenic Purpura ITP
Conditions
Keywords
Immune thrombocytopenic Purpura, Pediatric, Thrombocytopenia
Brief summary
This is an extension study designed to assess the safety and durability of platelet count increases with romiplostim treatment of thrombocytopenic patients with immune (Idiopathic) thrombocytopenia purpura. This study is available to pediatric patients who have completed a previous romiplostim ITP study and meet the eligibility criteria of this study.
Interventions
BIOLOGICALRomiplostim
Administered by subcutaneous injection once a week.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject or subject's legally acceptable representative has provided informed consent. * Subject completed a romiplostim study for the treatment of thrombocytopenia in pediatric subjects with ITP.
Exclusion criteria
* Subject has or previously had any bone marrow stem cell disorder (any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study). * Subject has any new active malignancy diagnosed since enrollment in the previous romiplostim ITP study. * Subject received any alkylating agents within four weeks before the screening visit or anticipated use during the time of the proposed study. * Other investigational medications are excluded. * Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) (with the exception of romiplostim in a previous clinical study). * Female subject of child bearing potential (defined as having first menses) is not willing to use highly effective contraception during treatment and for 4 weeks after the end of treatment. * Female subject is pregnant or breast feeding, or planning to become pregnant within 4 weeks after the end of treatment. * Subject has known sensitivity to any of the products to be administered during dosing. * Subject previously has entered this study (this will depend on the type of study). * Subject will not be available for protocol required study visits, to the best of the subject and investigator's knowledge. * Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose of study drug until 1 week after last dose. The median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks). | The adverse event (AE) severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The investigator assessed whether each adverse event was possibly related to the investigational product. |
| Duration Adjusted Rate of Treatment Emergent Adverse Events | From first dose of study drug until 1 week after last dose. The median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks). | Exposure adjusted rate was defined as the total number of events divided by the duration of time participants were under observation. The adverse event (AE) severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The investigator assessed whether each adverse event was possibly related to the study drug. |
| Number of Participants Who Developed Antibodies to Romiplostim | Once a year until the end of treatment and 1 week after the end of treatment; median (minimim, maximum) time on study was 34 (2, 91) months. | Two validated assays were used to test for antibodies to romiplostim / the thrombopoietin-mimetic peptide component of romiplostim (TMP). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies. Transient antibodies are those positive post-baseline but negative at the last time point tested. Persistent antibodies were those positive at the last time point tested. |
| Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Once a year until the end of treatment and 1 week after the end of treatment; median (minimim, maximum) time on study was 34 (2, 91) months. | Two validated assays were used to test for antibodies to endogenous thrombopoietin (TPO). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies. Transient antibodies are those positive post-baseline but negative at the last time point tested. Persistent antibodies were those positive at the last time point tested. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Platelet Response | Assessed every 4 weeks for the duration of treatment; the median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks). | Platelet response was defined as at least one platelet count ≥ 50 x 10\^9/L in the absence of rescue medication during the study. |
| Percentage of Participants Who Used Concomitant ITP Therapy | From baseline to the end of treatment; the median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks). | — |
Countries
Australia, Canada, Spain, United States
Participant flow
Recruitment details
This study was conducted at 28 centers in Australia, Canada, Spain, and the United States. Participants were enrolled from 30 December 2009 until 19 February 2015.
Pre-assignment details
Pediatric patients who completed a romiplostim study for the treatment of thrombocytopenia in pediatric subjects with immune (idiopathic) thrombocytopenia purpura (ITP) were eligible to participate in this study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study | 66 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Decision | 5 |
| Overall Study | Adverse Event | 1 |
| Overall Study | Noncompliance | 4 |
| Overall Study | Protocol Specified Criteria | 1 |
| Overall Study | Requirement for Alternative Therapy | 5 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 10.3 years STANDARD_DEVIATION 4.2 |
| Age, Customized Adolescents (12-17 years) | 28 Participants |
| Age, Customized Adults (18-64 years) | 1 Participants |
| Age, Customized Children (2-11 years) | 37 Participants |
| Race Aborigine | 0 Participants |
| Race American Indian or Alaska Native | 0 Participants |
| Race Asian | 6 Participants |
| Race Black or African American | 9 Participants |
| Race Hispanic or Latino | 9 Participants |
| Race Japanese | 0 Participants |
| Race Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race Other | 2 Participants |
| Race White or Caucasian | 40 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 65 |
| other Total, other adverse events | 64 / 65 |
| serious Total, serious adverse events | 19 / 65 |
Outcome results
Primary
Duration Adjusted Rate of Treatment Emergent Adverse Events
Exposure adjusted rate was defined as the total number of events divided by the duration of time participants were under observation. The adverse event (AE) severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The investigator assessed whether each adverse event was possibly related to the study drug.
Time frame: From first dose of study drug until 1 week after last dose. The median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks).
Population: Enrolled participants who received at least one dose of romiplostim.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | All adverse events (AEs) | 1397.2 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Serious adverse events | 29.7 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | AEs leading to discontinuation of study drug | 2.8 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | AEs leading to withdrawal from study | 0.6 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 3 adverse events | 38.5 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 4 adverse events | 6.6 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 5 adverse events | 0.0 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Treatment-related adverse events (TRAEs) | 24.2 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Serious treatment-related adverse events | 1.7 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | TRAEs leading to discontinuation of study drug | 0.0 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | TRAEs leading to withdrawal from study | 0.0 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 3 treatment-related adverse events | 2.8 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 4 treatment-related adverse events | 0.6 events per 100 subject-years |
| Romiplostim | Duration Adjusted Rate of Treatment Emergent Adverse Events | Grade 5 treatment-related adverse events | 0.0 events per 100 subject-years |
Primary
Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin
Two validated assays were used to test for antibodies to endogenous thrombopoietin (TPO). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies. Transient antibodies are those positive post-baseline but negative at the last time point tested. Persistent antibodies were those positive at the last time point tested.
Time frame: Once a year until the end of treatment and 1 week after the end of treatment; median (minimim, maximum) time on study was 34 (2, 91) months.
Population: Enrolled participants who received at least one dose of romiplostim with available postbaseline data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Binding antibodies to TPO | 2 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Transient binding antibodies to TPO | 2 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Persistent binding antibodies to TPO | 0 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Neutralizing antibodies to TPO | 0 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Transient neutralizing antibodies to TPO | 0 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Endogenous Thrombopoietin | Persistent neutralizing antibodies to TPO | 0 Participants |
Primary
Number of Participants Who Developed Antibodies to Romiplostim
Two validated assays were used to test for antibodies to romiplostim / the thrombopoietin-mimetic peptide component of romiplostim (TMP). The first was an immunoassay to confirm the presence of antibodies. The second was a cell-based bioassay to detect neutralizing or inhibitory effects in vitro. If a sample was positive in both assays, a participant was defined as positive for neutralizing antibodies. Transient antibodies are those positive post-baseline but negative at the last time point tested. Persistent antibodies were those positive at the last time point tested.
Time frame: Once a year until the end of treatment and 1 week after the end of treatment; median (minimim, maximum) time on study was 34 (2, 91) months.
Population: Enrolled participants who received at least one dose of romiplostim with available postbaseline data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Binding antibodies to romiplostim | 5 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Transient binding antibodies to romiplostim | 4 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Persistent binding antibodies to romiplostim | 1 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Neutralizing antibodies to romiplostim | 1 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Transient neutralizing antibodies to romiplostim | 0 Participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Persistent neutralizing antibodies to romiplostim | 1 Participants |
Primary
Number of Participants With Adverse Events
The adverse event (AE) severity grading scale used was the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE; Grade 5 = Death related to AE. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: * fatal * life threatening (places the subject at immediate risk of death) * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. The investigator assessed whether each adverse event was possibly related to the investigational product.
Time frame: From first dose of study drug until 1 week after last dose. The median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks).
Population: Enrolled participants who received at least one dose of romiplostim.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Romiplostim | Number of Participants With Adverse Events | Grade 5 adverse events | 0 Participants |
| Romiplostim | Number of Participants With Adverse Events | Treatment-related adverse events (TRAEs) | 17 Participants |
| Romiplostim | Number of Participants With Adverse Events | Treatment-related serious adverse events | 1 Participants |
| Romiplostim | Number of Participants With Adverse Events | TRAEs leading to discontinuation of study drug | 0 Participants |
| Romiplostim | Number of Participants With Adverse Events | TRAEs leading to withdrawal from study | 0 Participants |
| Romiplostim | Number of Participants With Adverse Events | Grade 3 treatment-related adverse events | 3 Participants |
| Romiplostim | Number of Participants With Adverse Events | Grade 4 treatment-related adverse events | 1 Participants |
| Romiplostim | Number of Participants With Adverse Events | Grade 5 treatment-related adverse events | 0 Participants |
| Romiplostim | Number of Participants With Adverse Events | All adverse events (AEs) | 64 Participants |
| Romiplostim | Number of Participants With Adverse Events | Serious adverse events | 19 Participants |
| Romiplostim | Number of Participants With Adverse Events | AEs leading to discontinuation of study drug | 2 Participants |
| Romiplostim | Number of Participants With Adverse Events | AEs leading to withdrawal from study | 1 Participants |
| Romiplostim | Number of Participants With Adverse Events | Grade 3 adverse events | 21 Participants |
| Romiplostim | Number of Participants With Adverse Events | Grade 4 adverse events | 5 Participants |
Secondary
Percentage of Participants Who Used Concomitant ITP Therapy
Time frame: From baseline to the end of treatment; the median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks).
Population: Enrolled participants who received at least one dose of romiplostim.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Romiplostim | Percentage of Participants Who Used Concomitant ITP Therapy | 47.7 percentage of participants | 95% Confidence Interval 35.1 |
Secondary
Percentage of Participants With a Platelet Response
Platelet response was defined as at least one platelet count ≥ 50 x 10\^9/L in the absence of rescue medication during the study.
Time frame: Assessed every 4 weeks for the duration of treatment; the median (minimum, maximum) duration of treatment was 135.0 weeks (5, 363 weeks).
Population: Enrolled participants who received at least one dose of romiplostim.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Romiplostim | Percentage of Participants With a Platelet Response | 93.8 percentage of participants | 95% Confidence Interval 85 |