MDS, Myelodysplastic Syndromes, Thrombocytopenia
Conditions
Keywords
MDS, Low Risk MDS, Intermediate-1 Risk MDS, Thrombocytopenia
Brief summary
The Data Monitoring Committee (DMC) for study 20060198 recommended that all subjects discontinue treatment of study drug and continue to be followed for long term follow-up. Amgen adopted the DMC recommendation.
Detailed description
This is a Phase 2, multicenter, randomized, double blind, placebo controlled study designed to assess the efficacy and safety of romiplostim (formerly, AMG 531) treatment in thrombocytopenic MDS patients. The study is composed of a 26-week placebo controlled test treatment period (romiplostim versus Placebo), a 4 week interim wash-out period, a 24-week placebo controlled extended treatment period, and a 4-week follow-up period followed by an End of Study (EOS) visit. During the interim wash-out period, a bone marrow biopsy will be performed in the absence of growth factor to assess changes in the marrow. In the extended treatment period, safety assessments will continue and participants will be allowed to receive any standard of care treatments for MDS. Patients will be followed for survival for an additional 60 months following the End of Study (EOS) visit.
Interventions
DRUGPlacebo
Placebo is supplied in a 5 mL single use glass vial as a sterile, white, preservative-free, lyophilized powder.
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
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
• Diagnosis of MDS using the World Health Organization (WHO) classification for myeloid neoplasms as assessed during the screening period. • Per MDS International Prognostic Scoring System (IPSS), low or intermediate-1 risk MDS as assessed during the screening period. • Mean of the 2 platelet counts taken within 4 weeks prior to randomization must be: - ≤ 20 x 10\^9/L, (with no individual count \>30 x 10\^9/L during the screening period), with or without history of bleeding associated with diagnosis of MDS, OR - ≤ 50 x 10\^9/L, (with no individual count \>60 x 10\^9/L during the screening period) with a history of bleeding associated with the diagnosis of MDS. • Patients must be ≥18 and ≤ 90 years of age at time of informed consent. Patients between 85 and 90 years of age must have been diagnosed with MDS ≤ 5 years from study start. • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. • Adequate liver function, as evidenced by alanine aminotransferase (ALT) ≤ 3 times laboratory normal range, aspartate aminotransferase (AST) ≤ 3 times laboratory normal range and total bilirubin ≤ 2.0 times laboratory normal range. (Adequate liver function for patients with confirmed diagnosis of Gilbert's Disease evidenced by ALT ≤ 3 times laboratory normal range, and AST ≤ 3 times laboratory normal range.) • Serum creatinine concentration ≤ 2 mg/dl (≤176.8 μmol/L). • Bone marrow biopsy and aspirate with cytogenetics within 3 months of starting first dose of investigational product. • Written Informed Consent.
Exclusion criteria
• Have ever received any disease-modifying treatment for MDS. • Previously diagnosed with intermediate-2 or high risk MDS using the IPSS. • Prior history of leukemia, aplastic anemia, or other non-MDS related bone marrow stem cell disorder. • Prior history of hematopoietic stem cell transplantation. • Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count \>1,000/μL) or known diagnosis of Chronic Myelomonocytic Leukemia per French-American-British Classification System for MDS (FAB) criteria. • Prior malignancy (other than in situ cervical cancer, non-melanoma skin cancer, or in situ carcinoma) unless treated with curative intent and without evidence of disease for ≥ 3 years before randomization. • Active or uncontrolled infections. • Unstable angina, congestive heart failure (New York Heart Association \[NYHA\] \> class II), uncontrolled hypertension (diastolic \>100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction. • History of arterial thrombosis (eg, stroke or transient ischemic attack) within the past year. • History of venous thrombosis that currently requires anti-coagulation therapy. • Received Interleukin (IL)-11 within 4 weeks of first dose of investigational product. • Have previously received any thrombopoietic growth factor. • Receipt of granulocyte-colony stimulating factor, (G-CSF), pegylated-G-CSF, or granulocyte macrophage-colony stimulating factor (GM-CSF) within 4 weeks of first dose of investigational product. • Planned receipt of peg-G-CSF or GM-CSF after first dose of investigational product. • Pregnant or breast feeding. • Patients of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator. Amgen recommends double barrier contraception is used for all applicable patients enrolled on this study. A double barrier method is defined as two methods of contraception, for example 2 actual barrier methods, or one actual barrier method and one hormonal method. • Patient has known sensitivity to any recombinant E coli-derived product (eg, Infergen®, Neupogen®, Somatropin, and Actimmune). • Previously enrolled into the 20060198 study or another romiplostim study. • Inability to comply with study procedures. • Patient currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinically Significant Bleeding Events | Test Treatment Period (Weeks 1-26) | A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified World Health Organization (WHO) bleeding scale: • Grade 0 = no bleeding • Grade 1 = petechia or mucosal or retinal bleeding not requiring intervention • Grade 2 = melena, hematemesis, hematuria, hemoptysis • Grade 3 = bleeding required red cell transfusion • Grade 4 = retinal bleeding with visual impairment • Grade 5 = non-fatal cerebral bleeding • Grade 6 = fatal cerebral bleeding • Grade 7 = fatal non-cerebral bleeding. Bleeding events that continue for more than 7 days were counted as separate events every eighth day. Multiple events that arose from one organ system on one day were collapsed into one single event. Bleeding events with a start date between the first dose date and the last dose date of the test treatment period+7 days are included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Overall Bleeding Events | Test Treatment Period (Weeks 1-26) | The time from first dose of study drug to the last dose of 26-week test treatment period. A bleeding event is defined as any bleeding event reported during the test treatment period. Bleeding events that continue for more than 7 days are counted as separate events every eighth day. Multiple events that arose from one organ system on one day are collapsed into one single event. Exposure adjusted event rate per 100 patient-years = events / patient-year \* 100). |
| Annualized Rate of Total Platelet Transfusion Units | Test Treatment Period (Weeks 1-26) | The time from first dose of study drug to the last dose of 26-week test treatment period. A unit of platelets is defined as a single pack of pooled platelet-rich plasma comprised of 6 to 8 individual platelet concentrate packs (200 to 400 mL), a single pack of pooled buffy-coat concentrate, or 1 apheresis (single donor) concentrate. Exposure adjusted event rate per 100 patient-years = events / patient-years \* 100. |
| Number of Participants With Platelet Hematologic Improvement (HI-P) | Test Treatment Period (Weeks 1-26) | Platelet Hematologic Improvemen defined by the international working group (IWG) as: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a patient starting with a platelet count of ≥ 20 x 10\^9/L or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a patient that started with a platelet count \< 20 x 10\^9/L. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. |
| Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions | Test Treatment Period (Weeks 1-26) | Duration for participants who did not report HI-P during the period is 0. A platelet hematologic improvement (HI-P) is defined by an MDS International Working criteria as patients with a baseline platelet count of ≥ 20 x 10\^9/L achieving an absolute increase of ≥ 30 x 10\^9/L or increasing the platelet count to above 20 x 10\^9/L and by at least 100% in patients with a baseline of \< 20 x 10\^9/L for at least 8 consecutive weeks. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. The durations of HI-P are cumulative if more than one incidence occurred. Exposure adjusted event rate per 100 patient-weeks = total number of weeks / patient-weeks \* 100. |
| Annualized Rate of Platelet Transfusion Events | Test Treatment Period (Weeks 1-26) | A discrete platelet transfusion is any number of platelet transfusion administered within a 3-day period. Transfusions administered more than 3 days apart are counted as separate events. Transfusion given in the absence of any bleeding, when platelet count is \>10x10\^9/L, is not counted as a platelet transfusion event. Events with start date between the first dose date and the last dose date of the test treatment period +7 days are included. Exposure adjusted event rate per 100 patient-years = (events / patient-years \* 100). Patient Year = total patient years of exposure to investigational product during 26 weeks test treatment period. |
| Time to Death | From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012. | Overall survival was calculated using Kaplan-Meier methods. For patients who discontinued early, additional information from the long term follow-up are added (closest available follow-up information up to 58 weeks). |
| Kaplan-Meier Estimate of Survival at Month 12 | Month 12, with a data cut-off date of 20 July 2012. | Overall survival was calculated using Kaplan-Meier methods. |
| Annualized Rate of Patient-reported Bleeding Events | Test Treatment Period (Weeks 1-26) | The number of bleeding events was obtained from the thrombocytopenia symptoms (Th-symptoms) survey. Patients reported spontaneous bleeding to have occurred 0, 1 or 2, 3 or 4, 5 or 6, or 7 or more times in the past week. The lower threshold of bleeding counts is used for conservative purposes (i.e., the 3 is used for the response option of 3 or 4 times). Exposure adjusted event rate per 100 patient-years = number of events / patient-year \* 100. |
| Number of Participants Who Died | From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012. | — |
Participant flow
Recruitment details
First Subject Enrolled: 21 July 2008, Last Subject Enrolled: 16 December 2010.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Weekly subcutaneous dosing with blinded matching placebo dose level for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. | 83 |
| Romiplostim Weekly subcutaneous dosing based on platelet count for 26 weeks during the Test Treatment Period and for 24 weeks during the Extended Treatment Period, separated by a 4-week interim washout period. Starting dose is at 750 μg, up to a maximum dose of 1000 μg, or reduced to a minimum of 250 μg. | 167 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 23 | 46 |
| Overall Study | Adverse Event | 4 | 20 |
| Overall Study | Death | 5 | 8 |
| Overall Study | Disease Progression | 0 | 8 |
| Overall Study | Ineligibility Determined | 1 | 2 |
| Overall Study | Lack of Efficacy | 9 | 11 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 6 | 11 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 22 |
Baseline characteristics
| Characteristic | Total | Romiplostim | Placebo |
|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 11.8 | 68.4 years STANDARD_DEVIATION 12 | 67 years STANDARD_DEVIATION 11.5 |
| Baseline Platelet Counts | 22.0 10^9/L STANDARD_DEVIATION 12 | 22.3 10^9/L STANDARD_DEVIATION 11.5 | 21.5 10^9/L STANDARD_DEVIATION 13 |
| International Prognostic Scoring System (IPSS) Total Score 0 | 63 Participants | 40 Participants | 23 Participants |
| International Prognostic Scoring System (IPSS) Total Score 0.5 | 124 Participants | 86 Participants | 38 Participants |
| International Prognostic Scoring System (IPSS) Total Score 1 | 54 Participants | 34 Participants | 20 Participants |
| International Prognostic Scoring System (IPSS) Total Score 1.5 | 1 Participants | 1 Participants | 0 Participants |
| International Prognostic Scoring System (IPSS) Total Score Missing | 8 Participants | 6 Participants | 2 Participants |
| Myelodysplastic Syndromes World Health Organization Classification MDS associated with isolated del 5Q | 0 Participants | 0 Participants | 0 Participants |
| Myelodysplastic Syndromes World Health Organization Classification MDS-U | 28 Participants | 16 Participants | 12 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RA | 11 Participants | 6 Participants | 5 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RAEB-1 | 33 Participants | 24 Participants | 9 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RAEB-2 | 1 Participants | 1 Participants | 0 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RARS | 2 Participants | 2 Participants | 0 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RCMD | 169 Participants | 114 Participants | 55 Participants |
| Myelodysplastic Syndromes World Health Organization Classification RCMD-RS | 6 Participants | 4 Participants | 2 Participants |
| Prior MDS Therapy No | 203 Participants | 133 Participants | 70 Participants |
| Prior MDS Therapy Yes | 47 Participants | 34 Participants | 13 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized White or Caucasian | 235 Participants | 156 Participants | 79 Participants |
| Sex: Female, Male Female | 102 Participants | 72 Participants | 30 Participants |
| Sex: Female, Male Male | 148 Participants | 95 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 74 / 82 | 146 / 168 |
| serious Total, serious adverse events | 22 / 82 | 67 / 168 |
Outcome results
Primary
Number of Clinically Significant Bleeding Events
A clinically significant bleeding event is defined as any bleeding event of grade ≥ 2 per the modified World Health Organization (WHO) bleeding scale: • Grade 0 = no bleeding • Grade 1 = petechia or mucosal or retinal bleeding not requiring intervention • Grade 2 = melena, hematemesis, hematuria, hemoptysis • Grade 3 = bleeding required red cell transfusion • Grade 4 = retinal bleeding with visual impairment • Grade 5 = non-fatal cerebral bleeding • Grade 6 = fatal cerebral bleeding • Grade 7 = fatal non-cerebral bleeding. Bleeding events that continue for more than 7 days were counted as separate events every eighth day. Multiple events that arose from one organ system on one day were collapsed into one single event. Bleeding events with a start date between the first dose date and the last dose date of the test treatment period+7 days are included.
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Clinically Significant Bleeding Events | 116 events |
| Romiplostim | Number of Clinically Significant Bleeding Events | 178 events |
p-value: 0.1395% CI: [0.66, 1.05]Anderson-Gill model
Secondary
Annualized Rate of Overall Bleeding Events
The time from first dose of study drug to the last dose of 26-week test treatment period. A bleeding event is defined as any bleeding event reported during the test treatment period. Bleeding events that continue for more than 7 days are counted as separate events every eighth day. Multiple events that arose from one organ system on one day are collapsed into one single event. Exposure adjusted event rate per 100 patient-years = events / patient-year \* 100).
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Overall Bleeding Events | 3786.4 events per 100 patient-years |
| Romiplostim | Annualized Rate of Overall Bleeding Events | 3459.9 events per 100 patient-years |
p-value: 0.02695% CI: [0.86, 0.99]Poisson regression model
Secondary
Annualized Rate of Patient-reported Bleeding Events
The number of bleeding events was obtained from the thrombocytopenia symptoms (Th-symptoms) survey. Patients reported spontaneous bleeding to have occurred 0, 1 or 2, 3 or 4, 5 or 6, or 7 or more times in the past week. The lower threshold of bleeding counts is used for conservative purposes (i.e., the 3 is used for the response option of 3 or 4 times). Exposure adjusted event rate per 100 patient-years = number of events / patient-year \* 100.
Time frame: Test Treatment Period (Weeks 1-26)
Population: The Patient Reported Outcomes (PRO) analysis set consists of patients in the full analysis set who also completed the baseline and at least one post-baseline assessment for any PRO measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Patient-reported Bleeding Events | 1995 events per 100 patient-years |
| Romiplostim | Annualized Rate of Patient-reported Bleeding Events | 1264 events per 100 patient-years |
p-value: <0.00195% CI: [0.57, 0.71]Poisson regression model
Secondary
Annualized Rate of Platelet Transfusion Events
A discrete platelet transfusion is any number of platelet transfusion administered within a 3-day period. Transfusions administered more than 3 days apart are counted as separate events. Transfusion given in the absence of any bleeding, when platelet count is \>10x10\^9/L, is not counted as a platelet transfusion event. Events with start date between the first dose date and the last dose date of the test treatment period +7 days are included. Exposure adjusted event rate per 100 patient-years = (events / patient-years \* 100). Patient Year = total patient years of exposure to investigational product during 26 weeks test treatment period.
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Platelet Transfusion Events | 1013.5 events per 100 patient-years |
| Romiplostim | Annualized Rate of Platelet Transfusion Events | 748.9 events per 100 patient-years |
p-value: <0.00195% CI: [0.66, 0.88]Poisson regression model
Secondary
Annualized Rate of Total Platelet Transfusion Units
The time from first dose of study drug to the last dose of 26-week test treatment period. A unit of platelets is defined as a single pack of pooled platelet-rich plasma comprised of 6 to 8 individual platelet concentrate packs (200 to 400 mL), a single pack of pooled buffy-coat concentrate, or 1 apheresis (single donor) concentrate. Exposure adjusted event rate per 100 patient-years = events / patient-years \* 100.
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized subjects
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Annualized Rate of Total Platelet Transfusion Units | 3120.2 units per 100 patient-years |
| Romiplostim | Annualized Rate of Total Platelet Transfusion Units | 2221.8 units per 100 patient-years |
p-value: <0.00195% CI: [0.68, 0.8]Poisson Regression model
Secondary
Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions
Duration for participants who did not report HI-P during the period is 0. A platelet hematologic improvement (HI-P) is defined by an MDS International Working criteria as patients with a baseline platelet count of ≥ 20 x 10\^9/L achieving an absolute increase of ≥ 30 x 10\^9/L or increasing the platelet count to above 20 x 10\^9/L and by at least 100% in patients with a baseline of \< 20 x 10\^9/L for at least 8 consecutive weeks. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint. The durations of HI-P are cumulative if more than one incidence occurred. Exposure adjusted event rate per 100 patient-weeks = total number of weeks / patient-weeks \* 100.
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions | 2.57 weeks per 100 patient-weeks |
| Romiplostim | Exposure-adjusted Total Duration of Platelet Hematologic Improvement (HI-P) in the Absence of Platelet Transfusions | 35.02 weeks per 100 patient-weeks |
p-value: 0.03295% CI: [1.03, 1.91]Poisson regression model
Secondary
Kaplan-Meier Estimate of Survival at Month 12
Overall survival was calculated using Kaplan-Meier methods.
Time frame: Month 12, with a data cut-off date of 20 July 2012.
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Kaplan-Meier Estimate of Survival at Month 12 | 78 percentage of participants |
| Romiplostim | Kaplan-Meier Estimate of Survival at Month 12 | 83 percentage of participants |
Secondary
Number of Participants Who Died
Time frame: From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Who Died | 17 participants |
| Romiplostim | Number of Participants Who Died | 30 participants |
Secondary
Number of Participants With Platelet Hematologic Improvement (HI-P)
Platelet Hematologic Improvemen defined by the international working group (IWG) as: an absolute increase in platelet count of ≥ 30 x 10\^9/L for a patient starting with a platelet count of ≥ 20 x 10\^9/L or an increase in platelet count from \< 20 x 10\^9/L to ≥ 20 x 10\^9/L and by at least 100% in a patient that started with a platelet count \< 20 x 10\^9/L. To account for any possible contribution from platelet transfusions, platelet counts within 3 days following administration of platelet transfusion is not counted towards the platelet hematologic improvement endpoint. If no platelet measurements are available on the weekly scheduled dose day, then that week is not counted towards the platelet hematologic improvement endpoint.
Time frame: Test Treatment Period (Weeks 1-26)
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Platelet Hematologic Improvement (HI-P) | 3 Participants |
| Romiplostim | Number of Participants With Platelet Hematologic Improvement (HI-P) | 61 Participants |
p-value: <0.00195% CI: [4.7, 51.8]Cochran-Mantel-Haenszel
Secondary
Time to Death
Overall survival was calculated using Kaplan-Meier methods. For patients who discontinued early, additional information from the long term follow-up are added (closest available follow-up information up to 58 weeks).
Time frame: From randomization to 58 weeks, the end of study visit or the closest available follow-up information up to 58 weeks from the long term follow-up for those who discontinued the study early, with a data cut-off date of 20 July 2012.
Population: Full analysis set includes all randomized patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Death | NA months |
| Romiplostim | Time to Death | NA months |