Eltrombopag Phase III Study In Chinese Chronic ITP Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01762761
First received: December 19, 2012
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

This randomized, double-blind and open-label phase III study is aimed to determine the efficacy, tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP) adult subjects. This study will be conducted in Chinese adult chronic ITP subjects who have not responded to or have relapsed after previous treatment for ITP, including first line therapy and /or splenectomy.

The primary objective of this study is to determine the efficacy of oral eltrombopag as a thrombopoietic agent treating previously treated chronic Chinese ITP patients comparing with placebo. The secondary objective is to assess the safety and tolerability of eltrombopag when administered for 6 weeks to previously treated adult chronic ITP patients comparing with the placebo. In addition, the long-term efficacy and safety of eltrombopag treatment will be also evaluated in the 24-week extension open-label phase after the double-blind phase as one of other study objectives. If the subject benefits from the eltrombopag treatment based on investigator's discretion, the subject can continue 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 will be embedded in this phase III study and conducted in the same patient population participated this phase III study.


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic and Hepatitis C
Drug: eltrombopag
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind and Open-label Phase III Study To Compare The Efficacy And Safety Of Eltrombopag With Placebo In Chinese Chronic ITP Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • platelet count [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with a platelet count ≥50×109/L after 42 days of dosing during the first 6 weeks of the double-blind randomized period (Stage 1) of the study.


Secondary Outcome Measures:
  • efficacy and safety of short term and long-term eltrombopag treatment [ Time Frame: 6 weeks, 6months and longer ] [ Designated as safety issue: Yes ]
    • To determine the efficacy and safety of oral eltrombopag as a thrombopoietic agent when administered once daily for 6 weeks and 6 months and longer to previously treated Chinese adult subjects with chronic ITP.

  • eltrombopag PK and PK/PD analysis [ Time Frame: 2nd week in open label stage ] [ Designated as safety issue: No ]
    • To characterize eltrombopag PK and describe the relationship between plasma eltrombopag exposure and platelet response (PK/PD) in Chinese subjects with chronic ITP.


Enrollment: 155
Study Start Date: February 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag
Thrombopoietin- receptor (TPO-R) agonist
Drug: eltrombopag
TPO-R agonist
Other Name: revolade
Placebo Comparator: Placebo
Placebo
Drug: placebo
placebo
Other Name: no other name

Detailed Description:

This randomized, double-blind and open-label phase III study is aimed to determine the efficacy, tolerance and safety of eltrombopag in Chinese chronic primary immune thrombocytopenia (ITP) adult subjects. This study will be conducted in Chinese adult chronic ITP subjects who have not responded to or have relapsed after previous treatment for ITP, including first line therapy and /or splenectomy.

The primary objective of this study is to determine the efficacy of oral eltrombopag as a thrombopoietic agent treating previously treated chronic Chinese ITP patients comparing with placebo. The secondary objective is to assess the safety and tolerability of eltrombopag when administered for 6 weeks to previously treated adult chronic ITP patients comparing with the placebo. In addition, the long-term efficacy and safety of eltrombopag treatment will be also evaluated in the 24-week extension open-label phase after the double-blind phase as one of other study objectives. If the subject benefits from the eltrombopag treatment based on investigator's discretion, the subject can continue 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 will be embedded in this phase III study and conducted in the same patient population participated this phase III study.

Approximately 150 eligible subjects will be randomized to either eltrombopag or matching placebo treatment in 2:1 ratio in stage 1(the 8-week double blind stage). Randomization for stage 1 will be stratified by splenectomy status (Yes/No), use of concomitant maintenance ITP therapy (Yes/No) and, baseline platelet count ( no more than 15×109/L, or >15×109/L). This study includes 3 stages. The stage 1 will be an 8-week double-blind, randomized, placebo-controlled treatment period. Following completion of Stage 1 and after completing the data clean for the initial 6 weeks, the investigator will be un-blinded to treatment assignment on an individual subject basis to enable appropriate starting dose selection for stage 2, a 24-week open-label treatment period. PK sampling and assessments will occur at the Week 2 visit during stage 2 of the study, when all subjects are receiving eltrombopag. After the completion of stage 2, subjects may continue the eltrombopag treatment in stage 3, if he/she can benefit from the continuous eltrombopag treatment based on investigator's judgement.

The initial dose of eltrombopag administration is 25 mg orally once daily. During the 8 weeks double-blind treatment, dose of investigational product will be adjusted according to the weekly subject platelet count.

The eligible subjects who have completed stage 1 (8 weeks of double-blind treatment period: the first 6 weeks data will be used for primary endpoint analysis and the last 2 weeks will be data clean period during which period the blinded treatment is continued as to the first 6 weeks) would enter a voluntary open-label stage 2 (24-week open-label extension phase) in which subjects from both eltrombopag group and placebo group will have the opportunity to receive eltrombopag treatment. Subjects unwilling or unqualified (such as the subjects who meet the stopping criteria) to participate in extension treatment will attend follow-up visits for 4 weeks after the completion of double-blind phase. During open-label stage 2 during which period all eligible subjects will receive open label eltrombopag treatment. The dose of eltrombopag will be continuously adjusted according to the subject's platelet count.

Following completion of Stage 2, if the subject benefits from the eltrombopag treatment based on investigator's discretion, the subject can voluntarily enter stage 3, during which the subject will continue eltrombopag treatment until the commercial launch of eltrombopag in China.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is ≥18 years old.
  2. Diagnosed with ITP for at least 12 months prior to screening, and have a platelet count of <30 X109/L on Day 1 (or within 48 hours prior to dosing on Day 1).
  3. Patients who have no response or relapsed after splenectomy. Or patients who have not been splenectomised and have either not responded to one or more prior therapies (except splenectomy), or who have relapsed prior therapy.
  4. Previous therapy for ITP including rescue must have been completed at least 2 weeks prior to randomization.
  5. Subjects treated with maintenance immunosuppressive therapy must be receiving a dose that has been stable for at least 1 month.
  6. No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) >450msec or QTc >480 for patients with a Bundle Branch Block.
  7. No history of clotting disorder, other than ITP.
  8. A complete blood count (CBC), within the reference range, with the following exceptions:

    • Platelets <30×109/L on Day 1 (or within 48hours of Day 1) is required for inclusion,
    • Hemoglobin: females and males 10.0 g/dl are eligible for inclusion,
    • Absolute neutrophil count (ANC) ≥1500/µL (1.5×109/L) is required for inclusion
  9. Blood chemistry test result no exceed normal by more than 20%. Total albumin must not be below the lower limit of normal (LLN) by more than 10%.
  10. Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study.

Exclusion Criteria:

  1. Patients with any prior history of arterial or venous thrombosis, AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, etc).
  2. Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
  3. Female subjects who are nursing or pregnant at screening or pre-dose on Day 1.
  4. History of alcohol/drug abuse or dependence within 12 months of the study.
  5. Treatment with thrombopoietin or an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
  6. Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
  7. Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks of the study start and until the end of the study.
  8. Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements, within 1 week of the study start.
  9. History of platelet aggregation that prevents reliable measurement of platelet counts.
  10. An abnormality in bone marrow examination result, other than ITP, identified on the screening examination, which in the opinion of the investigator makes the subject unsuitable for participation in the study (e.g. ≥MF-2 according to EU consensus scale [Thiele, 2005]) or suggests another primary diagnosis (e.g. Thrombocytopenia is secondary to another disease).
  11. Any laboratory or clinical evidence for HIV infection.
  12. Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
  13. Patients expected to require rescue on Day 1 of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01762761

Locations
China, Fujian
GSK Investigational Site
Fuzhou, Fujian, China, 350001
China, Guangdong
GSK Investigational Site
Guangzhou, Guangdong, China, 510515
GSK Investigational Site
Guangzhou, Guangdong, China, 510080
GSK Investigational Site
Zhongshan, Guangdong, China, 528403
China, Hunan
GSK Investigational Site
Changsha, Hunan, China, 410013
China, Jiangsu
GSK Investigational Site
Nanjing, Jiangsu, China, 210029
China, Jiangxi
GSK Investigational Site
Nanchang, Jiangxi, China, 330006
China, Shandong
GSK Investigational Site
Jianan, Shandong, China, 250012
China, Zhejiang
GSK Investigational Site
Hangzhou, Zhejiang, China, 310003
China
GSK Investigational Site
Beijing, China, 100730
GSK Investigational Site
Beijing, China, 100044
GSK Investigational Site
Beijing, China, 100083
GSK Investigational Site
Beijing, China, 100034
GSK Investigational Site
Chengdu, China, 610041
GSK Investigational Site
Jiang Su Province, China, 215006
GSK Investigational Site
Shanghai, China
GSK Investigational Site
Shanghai, China, 200025
GSK Investigational Site
Tianjin, China, 300020
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01762761     History of Changes
Other Study ID Numbers: 113765
Study First Received: December 19, 2012
Last Updated: June 26, 2014
Health Authority: China: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
eltrombopag
TPO-R agonist
Chronic ITP

Additional relevant MeSH terms:
Hepatitis C
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Purpura
Blood Coagulation Disorders
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on September 18, 2014