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NCT01762761

Eltrombopag Phase III Study In Chinese Chronic ITP Patients

Completed Phase 3 Results posted Last updated 3 December 2019
What this trial tests

Phase 3 trial testing eltrombopag in Purpura, Thrombocytopenic, Idiopathic and Hepatitis C in 155 participants. Completed in 22 November 2018.

Timeline
18 February 2013
Primary endpoint
5 June 2014
22 November 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment155
Start date18 February 2013
Primary completion5 June 2014
Estimated completion22 November 2018
Sites18 locations across China

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Purpura, Thrombocytopenic, Idiopathic and Hepatitis C. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants (Responders) Achieving a Platelet Count >=50×10^9/L After the First 6 Weeks of Stage 1 Primary · From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

The number of participants (responders) with platelet count \>=50x10\^9/L after 6 weeks of Stage 1 were compared between treatments using a logistic regression model adjusted for use of primary immune thrombocytopenia (ITP) medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15×10\^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6. Primary Analysis Data Set: a participant who withdrawals from Stage 1 or is emergently unblinded was classified as a negative response from the time o

GroupValue95% CI
Placebo3
Eltrombopag60
Number of Participants Achieving a Platelet Count >=50×10^9/L at Least Once During the First 6 Weeks of Stage 1 Secondary · From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

The number of participants (responders) with platelet count \>=50×10\^9/L at least once during the first 6 weeks of Stage 1 were compared between treatments using a logistic regression model adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15×10\^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.

GroupValue95% CI
Placebo9
Eltrombopag80
Number of Participants Achieving a Platelet Count >=30×10^9/L and at Least 2 Times the Baseline Platelet Count at Least Once During the 6 Weeks of Stage 1, the Whole Stage 2 and the Whole Stage 3 Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

The number of participants achieving a platelet count \>=30×10\^9/L and at least 2 times the Baseline platelet count at least once during the first 6 weeks of Stage 1 were analyzed. The Baseline platelet count is defined as the platelet count taken on Day 1 of the study or within 48 hours prior to the first dose of investigational product. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15×10\^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, We

Stage 1 (during the first 6 weeks)
GroupValue95% CI
Placebo18
Eltrombopag84
Stage 2 (during 24 weeks)
GroupValue95% CI
Placebo45
Eltrombopag81
Stage 3
GroupValue95% CI
Placebo36
Eltrombopag72
Number of Participants With Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss. The WHO Bleeding Scale were dichotomized to indicate no bleeding vs bleeding, i.e. 0=grade 0 and 1=grades 1, 2, 3 or 4. Generalized linear mixed model was applied with a Logit canonical link function for repeated binary data, allowing for Baseline dichotomized WHO bleeding grade, use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15×10\

Stage 1: Baseline
GroupValue95% CI
Placebo36
Eltrombopag68
Stage 1: Week 1
GroupValue95% CI
Placebo30
Eltrombopag43
Stage 1: Week 2
GroupValue95% CI
Placebo27
Eltrombopag32
Stage 1: Week 3
GroupValue95% CI
Placebo26
Eltrombopag29
Stage 1: Week 4
GroupValue95% CI
Placebo24
Eltrombopag23
Stage 1: Week 5
GroupValue95% CI
Placebo19
Eltrombopag24
Stage 1: Week 6
GroupValue95% CI
Placebo17
Eltrombopag17
Stage 2: Baseline
GroupValue95% CI
Placebo22
Eltrombopag64
Number of Participants With Clinically Significant Bleeding as Assessed Using the World Health Organization (WHO) Bleeding Scale Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss. The WHO Bleeding Scale grades were dichotomized into the following categories: no clinically significant bleeding = Grade 0 to 1; clinically significant bleeding = Grade 2 to 4. Generalized linear mixed model with a Logit canonical link function for repeated binary data, allowing for Baseline dichotomized WHO bleeding grade, use of ITP medication at Baseline (yes/no), splenecto

Stage 1: Baseline
GroupValue95% CI
Placebo5
Eltrombopag14
Stage 1:Week 1
GroupValue95% CI
Placebo5
Eltrombopag12
Stage 1: Week 2
GroupValue95% CI
Placebo4
Eltrombopag13
Stage 1: Week 3
GroupValue95% CI
Placebo6
Eltrombopag11
Stage 1: Week 4
GroupValue95% CI
Placebo5
Eltrombopag7
Stage 1: Week 5
GroupValue95% CI
Placebo2
Eltrombopag8
Stage 1: Week 6
GroupValue95% CI
Placebo4
Eltrombopag6
Stage 2: Baseline
GroupValue95% CI
Placebo3
Eltrombopag13
Time to Response Secondary · From the start of study treatment (Day 1) up to the end of Week 6 of Stage 1

Time to response is defined as time from the startin of treatment to the first time of achieving a platelet count \>=50x10\^9/L during the first 6 weeks of Stage 1. Time to response is summarized using Kaplan-Meier estimates and compared between treatment groups using a stratified log-rank test, stratifying for the use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15x10\^9/L (yes/no). The pike estimator of the treatment hazard ratio is based on the stratified log-rank test. Complete blood count including platelet count was done at Week 1, Week 2, Week

GroupValue95% CI
PlaceboNANA – NA
Eltrombopag3.143.00 – 4.14
Number of Participants Who Required Protocol-defined Rescue Treatment During the First 6 Weeks of Stage 1, Whole Stages 2 & 3 Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

Rescue treatment is defined as either a new ITP medication, an increase in dose of concomitant ITP medication from Baseline, a platelet transfusion, or a splenectomy. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15x10\^9/L (yes/no) and treatment.

Stage 1 (first 6 weeks)
GroupValue95% CI
Placebo17
Eltrombopag9
Stage 2
GroupValue95% CI
Placebo16
Eltrombopag14
Stage 3
GroupValue95% CI
Placebo13
Eltrombopag21
Number of Participants With a Platelet Count >=50×10^9/L During at Least 75% of Their Platelet Count Assessments Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

The number of participants with a platelet count \>=50×10\^9/L during at least 75% of their platelet count assessments was analyzed up to the end of Week 6 of Stage 1. Logistic regression analysis was adjusted for use of ITP medication at Baseline (yes/no), splenectomy (yes/no), Baseline platelet count \<=15x10\^9/L (yes/no) and treatment. Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.

Stage 1 (first 6 weeks)
GroupValue95% CI
Placebo1
Eltrombopag23
Stage 2
GroupValue95% CI
Placebo10
Eltrombopag38
Stage 3
GroupValue95% CI
Placebo13
Eltrombopag30
Total Duration of Time a Participant Had a Platelet Count >=50×10^9/L Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

Total duration of time a participant had platelet count \>=50 x 10\^9/L was analyzed using the van Elteren stratified rank test with stratification factors including the use of ITP medication at Baseline (yes/no), splenectomy (yes/no) and Baseline platelet count \<=15x10\^9/L (yes/no). Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.

Stage 1 (first 6 weeks)
GroupValue95% CI
Placebo0.000.00 – 5.1
Eltrombopag1.790.14 – 5.1
Stage 2
GroupValue95% CI
Placebo4.070.0 – 23.3
Eltrombopag7.290.0 – 24.6
Stage 3
GroupValue95% CI
Placebo27.000.0 – 227.4
Eltrombopag43.710.0 – 224.0
Maximum Period of Time a Participant Had a Platelet Count Continuously >= 50 ×10^9/L Secondary · From the start of study treatment (Day 1) up to the end of Stage 3

Maximum period of time a participant had a platelet count continously \>=50 x 10\^9/L was analyzed using the van Elteren stratified rank test with stratification factors including the use of ITP medication at Baseline (yes/no), splenectomy (yes/no) and Baseline platelet count \<=15x10\^9/L (yes/no). Complete blood count including platelet count was done at Week 1, Week 2, Week 3, Week 4, Week 5 and Week 6.

Stage 1 (first 6 weeks)
GroupValue95% CI
Placebo0.000.00 – 0.00
Eltrombopag1.570.14 – 3.07
Stage 2
GroupValue95% CI
Placebo2.710.0 – 23.3
Eltrombopag5.000.0 – 24.6
Stage 3
GroupValue95% CI
Placebo16.430.0 – 227.1
Eltrombopag28.140.0 – 227.1
Number of Participants That Reduced or Discontinued Baseline Concomitant ITP Medications During Stage 2 and Stage 3 Secondary · From the start of Stage 2 to the end of Stage 3

The number of participants taking concomitant ITP medications on Day 1 of Stage 1 who had a decrease in the dose or frequency of ITP medication or stopped ITP medication at any point during Stage 2 or Stage 3 will be presented. The Baseline concomitant ITP medication for Stage 2 and Stage 3 is defined as ITP medications taken prior to the first dose of investigational product of Stage 1. This study is still ongoing and this endpoint can only be analyzed when the stage 2 and stage 3 complete.

Stage 2
GroupValue95% CI
Placebo19
Eltrombopag20
Stage 3
GroupValue95% CI
Placebo5
Eltrombopag16
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Secondary · From the start of study treatment (Day 1) up to the end of Week 8 of Stage 1

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product.A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, is a congenital anomaly/birth defect or is associated with protocol specified liver injury and impaired liver function or is any protocol specific AEs.

Stage 1: Any AE
GroupValue95% CI
Placebo34
Eltrombopag66
Stage 1: Any SAE
GroupValue95% CI
Placebo5
Eltrombopag5
Stage 2: Any AE
GroupValue95% CI
Placebo43
Eltrombopag64
Stage 2: Any SAE
GroupValue95% CI
Placebo6
Eltrombopag11
Stage 3: any AE
GroupValue95% CI
Placebo38
Eltrombopag70
Stage 3: Any SAE
GroupValue95% CI
Placebo11
Eltrombopag21

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Event (AE) timeframe: Adverse events were collected from study start (form first dose of study treatment) until end of study treatment plus 30 days post-treatment, up to a maximum duration of approx. 70 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 17/51 (33%)
Deaths: 3/51
Eltrombopag
Serious: 33/104 (32%)
Deaths: 0/104

Serious adverse events (61 terms)

ReactionSystemPlaceboEltrombopag
CATARACTEye disorders
PLATELET COUNT DECREASEDInvestigations
CEREBRAL INFARCTIONNervous system disorders
THROMBOCYTOPENIABlood and lymphatic system disorders
ACUTE MYOCARDIAL INFARCTIONCardiac disorders
DEATHGeneral disorders
LUNG INFECTIONInfections and infestations
ACUTE KIDNEY INJURYRenal and urinary disorders
HAEMORRHAGIC ANAEMIABlood and lymphatic system disorders
IRON DEFICIENCY ANAEMIABlood and lymphatic system disorders
THROMBOCYTOPENIC PURPURABlood and lymphatic system disorders
THYROIDITIS SUBACUTEEndocrine disorders
CATARACT SUBCAPSULAREye disorders
LENTICULAR OPACITIESEye disorders
RETINOPATHYEye disorders
GASTRIC POLYPSGastrointestinal disorders
GASTRIC ULCERGastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders
HAEMORRHOIDSGastrointestinal disorders
HIATUS HERNIAGastrointestinal disorders
INTESTINAL OBSTRUCTIONGastrointestinal disorders
INTUSSUSCEPTIONGastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGEGastrointestinal disorders
CHEST DISCOMFORTGeneral disorders
CHOLECYSTITIS ACUTEHepatobiliary disorders
Other adverse events (43 terms — click to expand)

ReactionSystemPlaceboEltrombopag
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
NASOPHARYNGITISInfections and infestations
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
HYPOKALAEMIAMetabolism and nutrition disorders
URINARY TRACT INFECTIONInfections and infestations
BLOOD BILIRUBIN INCREASEDInvestigations
ANAEMIABlood and lymphatic system disorders
GAMMA-GLUTAMYLTRANSFERASE INCREASEDInvestigations
DIARRHOEAGastrointestinal disorders
BILIRUBIN CONJUGATED INCREASEDInvestigations
PHARYNGITISInfections and infestations
BLOOD BILIRUBIN UNCONJUGATED INCREASEDInvestigations
BLOOD GLUCOSE INCREASEDInvestigations
IRON DEFICIENCY ANAEMIABlood and lymphatic system disorders
HEADACHENervous system disorders
VISION BLURREDEye disorders
ABDOMINAL PAIN UPPERGastrointestinal disorders
TOOTHACHEGastrointestinal disorders
GINGIVITISInfections and infestations
NEUTROPHIL COUNT INCREASEDInvestigations
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
DIZZINESSNervous system disorders
COUGHRespiratory, thoracic and mediastinal disorders
RASHSkin and subcutaneous tissue disorders
BLOOD UREA INCREASEDInvestigations
WHITE BLOOD CELL COUNT INCREASEDInvestigations
ARTHRALGIAMusculoskeletal and connective tissue disorders
BACK PAINMusculoskeletal and connective tissue disorders
FATIGUEGeneral disorders
GINGIVAL BLEEDINGGastrointestinal disorders
OEDEMA PERIPHERALGeneral disorders
PYREXIAGeneral disorders
BLOOD CREATININE INCREASEDInvestigations
HYPERLIPIDAEMIAMetabolism and nutrition disorders
HYPERURICAEMIAMetabolism and nutrition disorders
PROTEINURIARenal and urinary disorders
PRURITUSSkin and subcutaneous tissue disorders
HYPERTENSIONVascular disorders
CHEST DISCOMFORTGeneral disorders

Most-reported serious reactions: CATARACT, PLATELET COUNT DECREASED, CEREBRAL INFARCTION, THROMBOCYTOPENIA, ACUTE MYOCARDIAL INFARCTION, DEATH, LUNG INFECTION, ACUTE KIDNEY INJURY.

Data from ClinicalTrials.gov NCT01762761 adverse events section.

Sponsor's own description

This randomized, double-blind and open-label phase III study aimed to determine the efficacy, tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP) adult subjects. This study was be conducted in Chinese adult chronic ITP subjects who had not responded to or had relapsed after previous treatment of ITP, including first line therapy and /or splenectomy. The primary objective of this study was to determine the efficacy of oral eltrombopag as a thrombopoietic agent treating previously treated chronic Chinese ITP patients compared to placebo. The secondary objective was to assess the safety and tolerability of eltrombopag when administered for 6 weeks to previously treated adult chronic ITP patients compared with placebo. In addition, the long-term efficacy and safety of eltrombopag treatment was also evaluated in the 24-week extension open-label phase after the double-blind phase as one of other study objectives. If the subject benefited from the eltrombopag treatment based on the investigator's discretion, the subject could continue on eltrombopag treatment until the commercial launch of eltrombopag in China. Furthermore, to understand the pharmacokinetics (PK) profile of eltrombopag and to explore the relationship between the PK and pharmacodynamics (PD) (platelet response), a PK/PD analysis was embedded in this phase III study and conducted in the same patient population who participated this phase III study.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia: stage 2 results from a multicenter phase III study.
    Liu X, Hou M, Li J, Li J, et al · · 2022 · cited 12× · PMID 33251910 · DOI 10.1080/09537104.2020.1847267
  2. Bridging the gaps between randomized controlled trials and real-world use of thrombopoietin receptor agonists for adult primary immune thrombocytopenia: a systematic review and meta-analysis.
    Luo L, Jin S, Song Z, Chong G, et al · · 2025 · PMID 41070063 · DOI 10.3389/fmed.2025.1667457

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