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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Eltrombopag is for oral use and comes in 25, 50 and 75 mg tablets. Prescribed dose is taken once daily.
Dexamethasone is for oral use and comes in 8 mg tablets. Prescribed dose is taken once daily.
Novartis Investigative Site
Aschaffenburg, Bavaria, Germany
Novartis Investigative Site
Aachen, Germany
Novartis Investigative Site
Chemnitz, Germany
Novartis Investigative Site
Donauwörth, Germany
Novartis Investigative Site
Dortmund, Germany
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Frankfurt, Germany
Novartis Investigative Site
Jena, Germany
Novartis Investigative Site
Kiel, Germany
Novartis Investigative Site
Kronach, Germany
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
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
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
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
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
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
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
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)
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)
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)
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
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.