Immune Thrombocytopenia (ITP)
Conditions
Keywords
ITP, Eltrombopag, Dexamethasone, Sustained response off treatment, TFR, Adult, ETB115, Platelets, Thrombocytopenic, Thrombopoietin receptor Agonist, Newly-diagnosed, Blood bleeding disorder
Brief summary
The purpose of this study was to compare the ability of eltrombopag in combination with a short course of high-dose dexamethasone to induce sustained response off treatment in patients with newly-diagnosed ITP versus 1-3 cycles of dexamethasone monotherapy. The unmet clinical need and the potential for eltrombopag when added to steroids to improve the treatment outcome and the potential to induce sustained response off treatment serve as the basis for clinical investigation of eltrombopag in first-line ITP.
Detailed description
This is a Phase II, multicenter, 1:1 randomized, open-label study that compared the efficacy and safety of eltrombopag in combination with a short course of high-dose dexamethasone to 1-3 cycles of high-dose dexamethasone monotherapy, as first-line treatment in adult patients with newly diagnosed ITP. Adult patients with newly diagnosed ITP who had platelet counts \< 30 × 10\^9/L and required treatment were screened, and if eligible, were randomized to either Arm A (eltrombopag in combination with a short course of dexamethasone) or Arm B (1-3 cycles of dexamethasone monotherapy). The study was conducted in the following periods: Screening Period: Patients were screened for 14 days based on the inclusion and exclusion criteria. Treatment Period: Arm A: Patients were treated for 26 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10\^9/L and maintained counts ≥ 30 × 10\^9/L during the tapering phase were eligible for treatment discontinuation. Duration of tapering before treatment discontinuation at Week 26 was 6 weeks. Arm B: Patients were treated up to 12 weeks during the treatment period. Patients who reached platelet counts ≥ 30 × 10\^9/L and maintained counts ≥ 30 × 10\^9/L after 1-3 cycles of dexamethasone treatment were eligible for treatment discontinuation. Patients with platelet counts \< 30 × 10\^9/L after 3 cycles of dexamethasone treatment were offered a course of eltrombopag treatment within the study and were discontinued from study at week 52. Observation period: After completion of the treatment period, all patients were observed for sustained response off treatment until week 52. Only patients with sustained response at week 52 were followed for another 26 weeks.
Interventions
DRUGEltrombopag
Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets. Prescribed dose is taken once daily.
DRUGDexamethasone
Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study. * Men and women ≥ 18 years of age * Newly diagnosed with primary ITP (time from diagnosis within 3 months) * Platelet count \< 30 × 109/L at screening and a need for treatment (per physician's discretion) Note: If pre-treatment is necessary, platelet count data performed directly before pre-treatment (can be used for study inclusion (screening value). Treatment-naïve patients will be included based on their platelet counts performed at screening
Exclusion criteria
* Previous history of treatment for ITP, except any ITP-directed therapy for a maximum of 3 days within 7 days before randomization * Patients with diagnosis of secondary thrombocytopenia * Patients who have life threatening bleeding complications per physician´s discretion * Patients with a history of thromboembolic events in the 6 months preceding enrollment or known risk factors for thromboembolism * Serum creatinine \> 1.5 mg/dL * Total bilirubin (TBIL) \> 1.5 × upper limit of normal (ULN) * Aspartate transaminase (AST) \> 3.0 × ULN * Alanine transaminase (ALT) \> 3.0 × ULN * Patients who are human immune deficiency virus (HIV),hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive * Patients with hepatic impairment (Child-Pugh score \> 5) * Patients with known active or uncontrolled infections not responding to appropriate therapy * History of current diagnosis of cardiac disease or impaired cardiac function denoted * Patients who have active malignancy * Patients with evidence of current alcohol/drug abuse * Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures * Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1 * Women of child-bearing potential and males unwilling to use adequate contraception during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Sustained Response Off Treatment at 52 Weeks | Study treatment discontinuation until week 52 | Sustained response off treatment at 52 weeks is defined as maintenance of platelet count ≥ 30 × 10\^9/L after treatment discontinuation until Week 52 in the absence of bleeding events ≥ Grade II or use of any rescue medication at all visits until Week 52. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Sustained Response Off Treatment | from last dose of study treatment until loss of response, approx. 52 weeks | Duration of sustained response off treatment is defined as time of treatment discontinuation until platelet count \< 30 × 109/L or bleeding events ≥ Grade II or use of any rescue therapy. If sustained response remains, the interval was censored with the date of the last platelet assessment. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding. |
| Overall Response by Week 4 | By Week 4 | Overall response by week 4 is defined as platelet count ≥ 30 × 109/L and ≥ 2 fold increase of screening platelet count and absence of bleeding and no rescue therapy within the first 4 weeks |
| Complete Response by Week 4 | By Week 4 | Complete Response by week 4 is defined as platelet count ≥ 100 × 109/L and absence of bleeding and no rescue therapy until week 4. |
| Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53 | Absolute change in platelet count from pre-treatment or screening to baseline (week 1) and from pre-treatment / screening to 2, 4, 13, 27 and 53 weeks. If pre-treatment was necessary before inclusion, platelet count data performed directly before pre-treatment were used for study inclusion (screening value to be used for inclusion/exclusion check and for analysis as a covariate). |
| Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53 | Relative change in platelet count from pre-treatment or screening to baseline (week 1) and from pre-treatment or screening to 2, 4, 13, 27, and 53 weeks. If pre-treatment was necessary before inclusion, platelet count data performed directly before pre-treatment were used for study inclusion (screening value to be used for inclusion/exclusion check and for analysis as a covariate). |
| Percentage of Patients With Overall Response at Week 52 | Study treatment discontinuation until week 52 | Overall response after treatment at week 52 was defined as maintenance of platelet count ≥ 30 x 109/L and ≥ 2-fold increase of screening platelet count after treatment discontinuation in the absence of bleeding event ≥ Grade II and no rescue therapy at all visits until Week 52. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding. |
| Time to Complete Response | Time from starting study treatment to achievement of complete response (up to 52 weeks) | Time to complete response is defined as time from starting study treatment to time of achievement of complete response. Complete response is defined as a platelet count ≥ 100 × 109/L and absence of bleeding and no rescue therapy. Results of time to complete response are reported per Kaplan-Meier estimates. |
| Duration of Overall Response (OR) and Complete Response (CR) | Achievement of overall or complete response until loss of response (up to 52 weeks) | Duration of overall or complete response (CR) is defined as time of achievement of overall or CR until loss of overall or CR. The duration of CR was calculated from the date of onset of CR until platelet count \< 100 x 109/L, or bleeding events ≥ Grade II (assessed by the modified World Health Organization (WHO) Bleeding Scale) or use of any rescue therapy, whatever was earlier. Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding. Results of duration of overall and complete response are reported per Kaplan-Meier estimates. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53 | The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) instrument is a 13-item validated tool used to measure an individual's level of fatigue during usual daily activities over the past 7 days. Items are scored on a 0-4 response scale (4=not at all to 0=very much) where the total possible score ranges from 0-52 (all items are summed up to create the total score); A score of less than 30 indicates severe fatigue. The higher scores represent better HRQoL. |
| Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53 | SF36 questionnaire is a tool to measure health-related QoL. SF36 questionnaires (physical and mental score) were answered throughout the study and is a validated instrument with 36 questions to measure general physical and mental health status via assessment of 8 domains-Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health-over the past 4 weeks. The SF36 is scored using norm-based scoring procedures and scores ranging from 0-100; higher values indicate less impairment, a higher QoL. In addition to this SAP-planned scoring score, an alternative scoring for both the physical SF36 score and the mental SF36 were performed by QualityMetric (QM) Incorporated, an IQVIA business. |
| Incidence and Severity of Bleeding Events | Baseline up to 52 weeks | Incidence and severity of bleeding assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Incidence of bleeding: participants had at least one bleeding event. Severity of bleeding: bleeding event is from grade 2 and higher |
| Time to Overall Response (TOR) | Time from starting study treatment to achievement of complete response (up to 52 weeks) | Time to overall response is defined as time from starting study treatment to time of achievement of overall response. Overall response is defined as a platelet count ≥ 30 × 10\^9/L and ≥ 2 fold increase of baseline platelet count and absence of bleeding and no rescue therapy censored with the last visit date for patients not achieving overall response. Results of TOR are reported per Kaplan-Meier estimates. |
Countries
Germany
Participant flow
Recruitment details
The study was conducted in 25 centers in Germany.
Pre-assignment details
Participants had to abstain from using investigational/marketed drugs and taking herbal supplements prior to taking the first dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Eltrombopag + Dexamethasone Patients were treated with eltrombopag in combination with a standard high-dose dexamethasone (1 cycle: 40 mg once daily (QD) from day 1-4) to induce sustained response off treatment. | 13 |
| Dexamethasone Patients were treated with a standard high-dose dexamethasone (1-3 cycles: 40 mg QD day 1-4 at 4 weeks intervals (or at 14-28 days intervals if needed) to induce sustained response off treatment. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-response | 1 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Dexamethasone | Total | Eltrombopag + Dexamethasone |
|---|---|---|---|
| Age, Continuous | 45.3 Years STANDARD_DEVIATION 14.3 | 53.0 Years STANDARD_DEVIATION 16.1 | 60.6 Years STANDARD_DEVIATION 14.5 |
| Race/Ethnicity, Customized Caucasian | 12 Participants | 24 Participants | 12 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 1 / 13 |
| other Total, other adverse events | 11 / 12 | 13 / 13 |
| serious Total, serious adverse events | 5 / 12 | 5 / 13 |
Outcome results
Primary
Percentage of Patients With Sustained Response Off Treatment at 52 Weeks
Sustained response off treatment at 52 weeks is defined as maintenance of platelet count ≥ 30 × 10\^9/L after treatment discontinuation until Week 52 in the absence of bleeding events ≥ Grade II or use of any rescue medication at all visits until Week 52. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding.
Time frame: Study treatment discontinuation until week 52
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eltrombopag + Dexamethasone | Percentage of Patients With Sustained Response Off Treatment at 52 Weeks | 2 Participants |
| Dexamethasone | Percentage of Patients With Sustained Response Off Treatment at 52 Weeks | 2 Participants |
p-value: 0.5133Regression, Logistic
Secondary
Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points
Absolute change in platelet count from pre-treatment or screening to baseline (week 1) and from pre-treatment / screening to 2, 4, 13, 27 and 53 weeks. If pre-treatment was necessary before inclusion, platelet count data performed directly before pre-treatment were used for study inclusion (screening value to be used for inclusion/exclusion check and for analysis as a covariate).
Time frame: Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization. Only patients who contributed data were included in the number analyzed per week. As not all participants contributed data for each visit the overall number of participants analyzed and the number analyzed per week differ.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 1 | 32.0 G/L | Standard Deviation 44.3 |
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 2 | 145.2 G/L | Standard Deviation 151.9 |
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 4 | 192.5 G/L | Standard Deviation 165.8 |
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 13 | 119.4 G/L | Standard Deviation 115.9 |
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 27 | 217.8 G/L | Standard Deviation 126.5 |
| Eltrombopag + Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 53 | 139.0 G/L | Standard Deviation 88 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 27 | 141.2 G/L | Standard Deviation 94.7 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 1 | 23.2 G/L | Standard Deviation 48 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 13 | 143.0 G/L | Standard Deviation 88.5 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 2 | 80.7 G/L | Standard Deviation 68.8 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 53 | 141.7 G/L | Standard Deviation 61.4 |
| Dexamethasone | Absolute Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 4 | 92.0 G/L | Standard Deviation 68.7 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire
The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) instrument is a 13-item validated tool used to measure an individual's level of fatigue during usual daily activities over the past 7 days. Items are scored on a 0-4 response scale (4=not at all to 0=very much) where the total possible score ranges from 0-52 (all items are summed up to create the total score); A score of less than 30 indicates severe fatigue. The higher scores represent better HRQoL.
Time frame: Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization. Only patients who contributed data were included in the number analyzed per week. As not all participants contributed data for each visit the overall number of participants analyzed and the number analyzed per week differ.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from Baseline (BL) to Week 2 | -4.2 scores on a scale | Standard Deviation 9.6 |
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week | 1.0 scores on a scale | Standard Deviation 4.4 |
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 5 | 1.2 scores on a scale | Standard Deviation 5 |
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 13 | 0.3 scores on a scale | Standard Deviation 8.3 |
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 27 | -3.6 scores on a scale | Standard Deviation 11 |
| Eltrombopag + Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 53 | 2.7 scores on a scale | Standard Deviation 5.6 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 27 | -3.1 scores on a scale | Standard Deviation 7.7 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from Baseline (BL) to Week 2 | -4.5 scores on a scale | Standard Deviation 6.9 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 13 | 0.3 scores on a scale | Standard Deviation 2.8 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week | -2.9 scores on a scale | Standard Deviation 5.1 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 53 | -3.4 scores on a scale | Standard Deviation 5.4 |
| Dexamethasone | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire | Change from BL to Week 5 | -5.1 scores on a scale | Standard Deviation 6.9 |
Secondary
Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM))
SF36 questionnaire is a tool to measure health-related QoL. SF36 questionnaires (physical and mental score) were answered throughout the study and is a validated instrument with 36 questions to measure general physical and mental health status via assessment of 8 domains-Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health-over the past 4 weeks. The SF36 is scored using norm-based scoring procedures and scores ranging from 0-100; higher values indicate less impairment, a higher QoL. In addition to this SAP-planned scoring score, an alternative scoring for both the physical SF36 score and the mental SF36 were performed by QualityMetric (QM) Incorporated, an IQVIA business.
Time frame: Baseline (Week 1), Week 2, 3, 5, 13, 27 and 53
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization. Only patients who contributed data were included in the number analyzed per week. As not all participants contributed data for each visit the overall number of participants analyzed and the number analyzed per week differ.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | Change from Baseline (CBL) to Wk 2: Physical Score (PS) | 1.9 scores on a scale | Standard Deviation 4.6 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: PS | 2.5 scores on a scale | Standard Deviation 5.8 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: PS | 1.5 scores on a scale | Standard Deviation 6.2 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 13: PS | 3.5 scores on a scale | Standard Deviation 9.9 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: PS | 2.6 scores on a scale | Standard Deviation 14.7 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: PS | 8.1 scores on a scale | Standard Deviation 11.8 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 2: Mental Score (MS) | -0.8 scores on a scale | Standard Deviation 6.1 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: MS | -2.0 scores on a scale | Standard Deviation 11 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: MS | 0.1 scores on a scale | Standard Deviation 7.3 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 13: MS | 3.3 scores on a scale | Standard Deviation 7.5 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: MS | -1.4 scores on a scale | Standard Deviation 4.9 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: MS | 2.1 scores on a scale | Standard Deviation 8.8 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 2: PS-QM | 2.0 scores on a scale | Standard Deviation 4.1 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: PS-QM | 3.4 scores on a scale | Standard Deviation 6.4 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: PS-QM | 2.4 scores on a scale | Standard Deviation 6 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 1: PS-QM | 4.1 scores on a scale | Standard Deviation 8.5 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: PS-QM | 3.6 scores on a scale | Standard Deviation 12.4 |
| Eltrombopag + Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: PS-QM | 6.2 scores on a scale | Standard Deviation 10.7 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: PS-QM | -1.4 scores on a scale | Standard Deviation 7.8 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | Change from Baseline (CBL) to Wk 2: Physical Score (PS) | -3.3 scores on a scale | Standard Deviation 6.6 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 13: MS | 4.1 scores on a scale | Standard Deviation 7.4 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: PS | -1.4 scores on a scale | Standard Deviation 8.8 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: PS-QM | 0.2 scores on a scale | Standard Deviation 9.4 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: PS | -2.7 scores on a scale | Standard Deviation 10.5 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: MS | -2.7 scores on a scale | Standard Deviation 7.4 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 13: PS | 0.3 scores on a scale | Standard Deviation 8 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: PS-QM | -2.7 scores on a scale | Standard Deviation 8.5 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: PS | -0.9 scores on a scale | Standard Deviation 10.8 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: MS | 0.6 scores on a scale | Standard Deviation 5.7 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 53: PS | 0.3 scores on a scale | Standard Deviation 10 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 27: PS-QM | -1.0 scores on a scale | Standard Deviation 9.7 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 2: Mental Score (MS) | -1.2 scores on a scale | Standard Deviation 7.6 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 2: PS-QM | -3.3 scores on a scale | Standard Deviation 6 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 3: MS | -1.6 scores on a scale | Standard Deviation 9.7 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 1: PS-QM | 0.3 scores on a scale | Standard Deviation 7.6 |
| Dexamethasone | Change From Baseline in Short Form 36 Health Survey (SF-36v2) Questionnaire (Physical (PS), Mental Score (MS) and Alternative Scoring (PS-QM)) | CBL to Week 5: MS | -1.7 scores on a scale | Standard Deviation 11.5 |
Secondary
Complete Response by Week 4
Complete Response by week 4 is defined as platelet count ≥ 100 × 109/L and absence of bleeding and no rescue therapy until week 4.
Time frame: By Week 4
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eltrombopag + Dexamethasone | Complete Response by Week 4 | 8 Participants |
| Dexamethasone | Complete Response by Week 4 | 9 Participants |
Secondary
Duration of Overall Response (OR) and Complete Response (CR)
Duration of overall or complete response (CR) is defined as time of achievement of overall or CR until loss of overall or CR. The duration of CR was calculated from the date of onset of CR until platelet count \< 100 x 109/L, or bleeding events ≥ Grade II (assessed by the modified World Health Organization (WHO) Bleeding Scale) or use of any rescue therapy, whatever was earlier. Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding. Results of duration of overall and complete response are reported per Kaplan-Meier estimates.
Time frame: Achievement of overall or complete response until loss of response (up to 52 weeks)
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization. Patients who did not reach OR/CR were censored at time 0.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Eltrombopag + Dexamethasone | Duration of Overall Response (OR) and Complete Response (CR) | Median duration of overall response | 8.3 Weeks |
| Eltrombopag + Dexamethasone | Duration of Overall Response (OR) and Complete Response (CR) | Median duration of complete response | 9.7 Weeks |
| Dexamethasone | Duration of Overall Response (OR) and Complete Response (CR) | Median duration of overall response | 3.6 Weeks |
| Dexamethasone | Duration of Overall Response (OR) and Complete Response (CR) | Median duration of complete response | 1.3 Weeks |
Secondary
Duration of Sustained Response Off Treatment
Duration of sustained response off treatment is defined as time of treatment discontinuation until platelet count \< 30 × 109/L or bleeding events ≥ Grade II or use of any rescue therapy. If sustained response remains, the interval was censored with the date of the last platelet assessment. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding.
Time frame: from last dose of study treatment until loss of response, approx. 52 weeks
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization and who had a response.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eltrombopag + Dexamethasone | Duration of Sustained Response Off Treatment | 49.1 Weeks | Standard Deviation 0 |
| Dexamethasone | Duration of Sustained Response Off Treatment | 45.7 Weeks | Standard Deviation 2.8 |
Secondary
Incidence and Severity of Bleeding Events
Incidence and severity of bleeding assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Incidence of bleeding: participants had at least one bleeding event. Severity of bleeding: bleeding event is from grade 2 and higher
Time frame: Baseline up to 52 weeks
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eltrombopag + Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events | 10 Participants |
| Eltrombopag + Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events with severity: ≥ grade 2 | 6 Participants |
| Eltrombopag + Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events with severity: ≥ grade 3 | 2 Participants |
| Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events | 12 Participants |
| Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events with severity: ≥ grade 2 | 2 Participants |
| Dexamethasone | Incidence and Severity of Bleeding Events | Incidence of Bleeding events with severity: ≥ grade 3 | 1 Participants |
Secondary
Overall Response by Week 4
Overall response by week 4 is defined as platelet count ≥ 30 × 109/L and ≥ 2 fold increase of screening platelet count and absence of bleeding and no rescue therapy within the first 4 weeks
Time frame: By Week 4
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eltrombopag + Dexamethasone | Overall Response by Week 4 | 10 Participants |
| Dexamethasone | Overall Response by Week 4 | 11 Participants |
Secondary
Percentage of Patients With Overall Response at Week 52
Overall response after treatment at week 52 was defined as maintenance of platelet count ≥ 30 x 109/L and ≥ 2-fold increase of screening platelet count after treatment discontinuation in the absence of bleeding event ≥ Grade II and no rescue therapy at all visits until Week 52. Bleeding events ≥ Grade II are assessed by the modified World Health Organization (WHO) Bleeding Scale; Bleeding is graded based on a 1-4 scale (1=minor bleeding to 4=severe bleeding). Characteristics of bleeding events ≥ Grade II include: epistaxis ≥30 minutes, large purpura, joint bleeding, melanotic stool, hematemesis, gross hematuria, abnormal vaginal bleeding, hemoptysis, Visible blood in body cavity fluid, retinal bleeding, bleeding at invasive sites, bleeding requiring transfusion, bleeding associated with moderate or severe hemodynamic instability, fatal bleeding, CNS bleeding.
Time frame: Study treatment discontinuation until week 52
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eltrombopag + Dexamethasone | Percentage of Patients With Overall Response at Week 52 | 2 Participants |
| Dexamethasone | Percentage of Patients With Overall Response at Week 52 | 2 Participants |
p-value: 0.5133Regression, Logistic
Secondary
Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points
Relative change in platelet count from pre-treatment or screening to baseline (week 1) and from pre-treatment or screening to 2, 4, 13, 27, and 53 weeks. If pre-treatment was necessary before inclusion, platelet count data performed directly before pre-treatment were used for study inclusion (screening value to be used for inclusion/exclusion check and for analysis as a covariate).
Time frame: Pre-treatment/screening, Week 1 (baseline), 2, 4, 13, 27, and 53
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization. Only patients who contributed data were included in the number analyzed per week. As not all participants contributed data for each visit the overall number of participants analyzed and the number analyzed per week differ.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 2 | 5795.5 Percentage change in platelet counts | Standard Deviation 9672.4 |
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 13 | 8050.6 Percentage change in platelet counts | Standard Deviation 12277.8 |
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 1 | 347.9 Percentage change in platelet counts | Standard Deviation 486.8 |
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 27 | 13667.9 Percentage change in platelet counts | Standard Deviation 15717.1 |
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 4 | 11400.9 Percentage change in platelet counts | Standard Deviation 16875.2 |
| Eltrombopag + Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 53 | 9392.3 Percentage change in platelet counts | Standard Deviation 11476 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 4 | 2865.4 Percentage change in platelet counts | Standard Deviation 3805.4 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 1 | 293.4 Percentage change in platelet counts | Standard Deviation 418.4 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 2 | 2028.2 Percentage change in platelet counts | Standard Deviation 4382 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 53 | 5612.1 Percentage change in platelet counts | Standard Deviation 8300.7 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 13 | 4725.7 Percentage change in platelet counts | Standard Deviation 8418.2 |
| Dexamethasone | Relative Change in Platelet Count From Pre-treatment/Screening to Baseline and to Various Time Points | Week 27 | 4381.1 Percentage change in platelet counts | Standard Deviation 8195.2 |
Secondary
Time to Complete Response
Time to complete response is defined as time from starting study treatment to time of achievement of complete response. Complete response is defined as a platelet count ≥ 100 × 109/L and absence of bleeding and no rescue therapy. Results of time to complete response are reported per Kaplan-Meier estimates.
Time frame: Time from starting study treatment to achievement of complete response (up to 52 weeks)
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eltrombopag + Dexamethasone | Time to Complete Response | 1.1 Weeks |
| Dexamethasone | Time to Complete Response | 2.1 Weeks |
Secondary
Time to Overall Response (TOR)
Time to overall response is defined as time from starting study treatment to time of achievement of overall response. Overall response is defined as a platelet count ≥ 30 × 10\^9/L and ≥ 2 fold increase of baseline platelet count and absence of bleeding and no rescue therapy censored with the last visit date for patients not achieving overall response. Results of TOR are reported per Kaplan-Meier estimates.
Time frame: Time from starting study treatment to achievement of complete response (up to 52 weeks)
Population: The Full Analysis Set (FAS) consists of all patients to whom study treatment has been assigned by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eltrombopag + Dexamethasone | Time to Overall Response (TOR) | 1.1 Weeks |
| Dexamethasone | Time to Overall Response (TOR) | 1.0 Weeks |