Idiopathic Thrombocytopenic Purpura, Thrombocytopenia
Conditions
Keywords
Immune (Idiopathic) Thrombocytopenic Purpura (ITP), Thrombocytopenic
Brief summary
The purpose of this study is to determine the safety of romiplostim as a long-term treatment in thrombocytopenic subjects with ITP, to evaluate the long-term platelet response to romiplostim, and to evaluate changes in patient reported outcomes due to the use of romiplostim. Participants must have previously completed a romiplostim ITP study.
Interventions
BIOLOGICALRomiplostim
Romiplostim is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have previously completed a romiplostim ITP study * Platelet count ≤ 50 x 10 \^9/L * Written informed consent
Exclusion criteria
* Bone marrow stem cell disorder or new active malignancies diagnosed since enrollment in the previous romiplostim ITP study * Received any alkylating agents within 4 weeks before screening visit or anticipated use during the time of the proposed study * Currently enrolled in or has not yet completed at least 4 weeks since ending device or drug trial(s) (other than the previous romiplostim ITP study), or subject is receiving other investigational agent(s) other than romiplostim * Not using adequate contraceptive precautions * Not available for follow-up assessments * Has any kind of disorder that compromises the ability of the participant to give informed consent and does not have a legally-acceptable representative and/or is unable to comply with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Duration of treatment plus 8 weeks (up to 285 weeks) | Participants with one or more occurrences of one or more adverse events up to 8 weeks after the end of treatment. Participants with more than one event were only counted once. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Reduction or Discontinuation of Concurrent ITP Therapies | Duration of treatment (up to 277 weeks) | The number of participants with a reduction or discontinuation of concurrent immune (idiopathic) thrombocytopenic purpura (ITP) therapies (corticosteroids, danazol, azathioprine) during the study. |
| Change From Baseline in ITP Patient Assessment Questionnaire | Baseline to Week 48 | The ITP Patient Assessment Questionnaire (ITP-PAQ) assesses ITP-specific health-related quality of life (HRQOL). This questionnaire assesses ITP specific health-related quality of life (HRQOL). The questionnaire consists of 44 items and has six domains: These domains assess the impact of ITP on Physical Health, Mental Health, Work, Social Activity, Women's Health and Overall QOL. The impact of ITP on Physical Health consists of four sub-scales, which evaluate ITP related Symptoms, Fatigue, Bother and Activity. The impact of ITP on Mental Health consists of two sub-scales, which evaluate Psychological distress and Fear in a population with ITP. Items are scored from 0-100 with higher scores indicating better HRQOL. |
| Change From Baseline in Short Form 36 (SF-36) | Baseline to Week 48 | The SF-36 is a widely used generic health-related quality of life measure. It has 36 questions with 8 domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Items are scored from 0 to 100 with higher scores indicating better health status. |
| Number of Participants With a Platelet Response | Duration of treatment (up to 277 weeks) | Platelet response was defined as having a platelet count of ≥ 50 x 10\^9/L at any time on study, excluding platelet counts within 8 weeks after receiving any rescue medications. |
| Change From Baseline in Euroqol-5D (EQ-5D) Visual Analogue Scale (VAS) | Baseline to Week 48 | The EQ-5D is a patient-completed, multidimensional measure of health related quality of life. The EQ-5D VAS records the respondent's self-rated health status on a vertical graduated (0-100) visual analogue scale. Higher EQ-5D VAS scores represent better health status. |
| Patient Global Assessment | Week 1 and Week 48 | The Patient Global Assessment is two questions which assess the overall health-related quality of life (HRQOL) and symptoms of the patient. Each item is answered on a 15-point Likert scale ranging from 'A very great deal worse' (1) to 'A very great deal better' (15). A higher score indicates that quality of life or symptoms have improved. |
| Change From Baseline in Euroqol-5D (EQ-5D) Index Score | Baseline to Week 48 | The EQ-5D is a patient-completed, multidimensional measure of health related quality of life. The instrument is applicable to a wide range of health conditions and treatments and results in a single index score and a visual analog scale (VAS) score. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension comprises three levels (no problems, some/moderate problems, extreme problems). A unique EQ-5D health state is defined by combining one level from each of the five dimensions. EQ-5D index values range from -0.59 to 1.00. Higher EQ-5D Index scores represent better health status. |
Participant flow
Recruitment details
Participants were enrolled from 2 August 2004 through 15 April 2009
Participants by arm
| Arm | Count |
|---|---|
| Romiplostim in Adults Romiplostim administered to adult participants subcutaneously weekly at doses up to 30 µg/kg based on platelet counts. After Amendment 1 the maximum weekly dose was reduced to 15 µg/kg, and after Amendment 2 the maximum weekly dose was reduced to 10 µg/kg. However, participants enrolled prior to Amendment 2 who were receiving \>10 µg/kg were permitted to remain on that higher dose, but could not increase their dose. In addition, if the participant's dose was decreased, it could not be increased to \>10 µg/kg. | 292 |
| Romiplostim in Pediatric Population Romiplostim administered to pediatric participants subcutaneously weekly at doses up to 10 µg/kg based on platelet counts. | 21 |
| Total | 313 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 0 |
| Overall Study | Death | 15 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Noncompliance | 3 | 1 |
| Overall Study | Other | 11 | 0 |
| Overall Study | Physician Decision | 7 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol deviation | 1 | 0 |
| Overall Study | Protocol-specified criteria | 3 | 0 |
| Overall Study | Requirement for alternative therapy | 11 | 1 |
| Overall Study | Withdrawal by Subject | 26 | 2 |
Baseline characteristics
| Characteristic | Romiplostim in Adults | Romiplostim in Pediatric Population | Total |
|---|---|---|---|
| Age, Continuous | 54.2 Years STANDARD_DEVIATION 16.9 | 10.2 Years STANDARD_DEVIATION 5.1 | 51.3 Years STANDARD_DEVIATION 19.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants | 3 Participants | 16 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 21 Participants | 4 Participants | 25 Participants |
| Race/Ethnicity, Customized Japanese | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 246 Participants | 13 Participants | 259 Participants |
| Sex: Female, Male Female | 184 Participants | 6 Participants | 190 Participants |
| Sex: Female, Male Male | 108 Participants | 15 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 270 / 291 | 18 / 20 |
| serious Total, serious adverse events | 117 / 291 | 2 / 20 |
Outcome results
Primary
Number of Participants With Adverse Events
Participants with one or more occurrences of one or more adverse events up to 8 weeks after the end of treatment. Participants with more than one event were only counted once.
Time frame: Duration of treatment plus 8 weeks (up to 285 weeks)
Population: Safety Analysis Set, composed of all participants who received at least one dose of romiplostim
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim in Adults | Number of Participants With Adverse Events | 284 Participants |
| Romiplostim in Pediatric Population | Number of Participants With Adverse Events | 19 Participants |
Secondary
Change From Baseline in Euroqol-5D (EQ-5D) Index Score
The EQ-5D is a patient-completed, multidimensional measure of health related quality of life. The instrument is applicable to a wide range of health conditions and treatments and results in a single index score and a visual analog scale (VAS) score. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension comprises three levels (no problems, some/moderate problems, extreme problems). A unique EQ-5D health state is defined by combining one level from each of the five dimensions. EQ-5D index values range from -0.59 to 1.00. Higher EQ-5D Index scores represent better health status.
Time frame: Baseline to Week 48
Population: Full analysis set with available data. Patient reported outcomes were only analyzed in adult participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim in Adults | Change From Baseline in Euroqol-5D (EQ-5D) Index Score | 0.03 scores on a scale | Standard Deviation 0.16 |
Secondary
Change From Baseline in Euroqol-5D (EQ-5D) Visual Analogue Scale (VAS)
The EQ-5D is a patient-completed, multidimensional measure of health related quality of life. The EQ-5D VAS records the respondent's self-rated health status on a vertical graduated (0-100) visual analogue scale. Higher EQ-5D VAS scores represent better health status.
Time frame: Baseline to Week 48
Population: Full analysis set with available data. Patient reported outcomes were only analyzed in adult participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim in Adults | Change From Baseline in Euroqol-5D (EQ-5D) Visual Analogue Scale (VAS) | 6.05 scores on a scale | Standard Deviation 14.85 |
Secondary
Change From Baseline in ITP Patient Assessment Questionnaire
The ITP Patient Assessment Questionnaire (ITP-PAQ) assesses ITP-specific health-related quality of life (HRQOL). This questionnaire assesses ITP specific health-related quality of life (HRQOL). The questionnaire consists of 44 items and has six domains: These domains assess the impact of ITP on Physical Health, Mental Health, Work, Social Activity, Women's Health and Overall QOL. The impact of ITP on Physical Health consists of four sub-scales, which evaluate ITP related Symptoms, Fatigue, Bother and Activity. The impact of ITP on Mental Health consists of two sub-scales, which evaluate Psychological distress and Fear in a population with ITP. Items are scored from 0-100 with higher scores indicating better HRQOL.
Time frame: Baseline to Week 48
Population: Full analysis set with available data. Patient reported outcomes were only analyzed in adult participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Physical Health Symptoms (N=209) | 4.20 scores on a scale | Standard Deviation 13.15 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Physical Health Fatigue (N=208) | 3.99 scores on a scale | Standard Deviation 16 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Physical Health Bother (N=204) | 6.43 scores on a scale | Standard Deviation 17.39 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Physical Health Activity (N=208) | 5.23 scores on a scale | Standard Deviation 21.08 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Emotional Health Psychological (N=208) | 4.01 scores on a scale | Standard Deviation 15.81 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Emotional Health Fear (N=209) | 3.48 scores on a scale | Standard Deviation 12.59 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Overall Quality of Life (N=210) | 8.32 scores on a scale | Standard Deviation 19.65 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Social Quality of Life (N=209) | 3.89 scores on a scale | Standard Deviation 13.41 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Women's Reproductive Health (N=71) | 4.51 scores on a scale | Standard Deviation 16.35 |
| Romiplostim in Adults | Change From Baseline in ITP Patient Assessment Questionnaire | Work Quality of Life (N=75) | 2.78 scores on a scale | Standard Deviation 14.54 |
Secondary
Change From Baseline in Short Form 36 (SF-36)
The SF-36 is a widely used generic health-related quality of life measure. It has 36 questions with 8 domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Items are scored from 0 to 100 with higher scores indicating better health status.
Time frame: Baseline to Week 48
Population: Full analysis set with available data. Patient reported outcomes were only analyzed in adult participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Physical Functioning (N=206) | 1.38 scores on a scale | Standard Deviation 6.34 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Role-Physical (N=208) | 2.03 scores on a scale | Standard Deviation 8.89 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Bodily Pain (N=206) | 0.94 scores on a scale | Standard Deviation 7.99 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | General Health Perception (N=208) | 1.31 scores on a scale | Standard Deviation 7.03 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Vitality (N=208) | 1.68 scores on a scale | Standard Deviation 7.47 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Social Functioning (N=208) | 0.52 scores on a scale | Standard Deviation 8.21 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Role-Emotional (N=205) | 1.75 scores on a scale | Standard Deviation 12.22 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Mental Health Index (N=208) | 0.91 scores on a scale | Standard Deviation 7.45 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Physical Component Summary (N=200) | 1.49 scores on a scale | Standard Deviation 6.51 |
| Romiplostim in Adults | Change From Baseline in Short Form 36 (SF-36) | Mental Component Summary (N=200) | 1.06 scores on a scale | Standard Deviation 8.8 |
Secondary
Number of Participants With a Platelet Response
Platelet response was defined as having a platelet count of ≥ 50 x 10\^9/L at any time on study, excluding platelet counts within 8 weeks after receiving any rescue medications.
Time frame: Duration of treatment (up to 277 weeks)
Population: Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim in Adults | Number of Participants With a Platelet Response | 275 Participants |
| Romiplostim in Pediatric Population | Number of Participants With a Platelet Response | 20 Participants |
Secondary
Number of Participants With a Reduction or Discontinuation of Concurrent ITP Therapies
The number of participants with a reduction or discontinuation of concurrent immune (idiopathic) thrombocytopenic purpura (ITP) therapies (corticosteroids, danazol, azathioprine) during the study.
Time frame: Duration of treatment (up to 277 weeks)
Population: Subset of Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim and with baseline concurrent ITP therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim in Adults | Number of Participants With a Reduction or Discontinuation of Concurrent ITP Therapies | 30 Participants |
| Romiplostim in Pediatric Population | Number of Participants With a Reduction or Discontinuation of Concurrent ITP Therapies | 1 Participants |
Secondary
Patient Global Assessment
The Patient Global Assessment is two questions which assess the overall health-related quality of life (HRQOL) and symptoms of the patient. Each item is answered on a 15-point Likert scale ranging from 'A very great deal worse' (1) to 'A very great deal better' (15). A higher score indicates that quality of life or symptoms have improved.
Time frame: Week 1 and Week 48
Population: Full analysis set with available data. Patient reported outcomes were only analyzed in adult participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Romiplostim in Adults | Patient Global Assessment | Week 1 (N=271) | 7.61 scores on a scale | Standard Deviation 2.02 |
| Romiplostim in Adults | Patient Global Assessment | Week 48 (N=216) | 8.18 scores on a scale | Standard Deviation 1.78 |