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to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia With Chronic HBV Infection

Primary Purpose

Thrombocytopenia Purpura, Chronic HBV Infection

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Eltrombopag

About this trial

This is an interventional treatment trial for Thrombocytopenia Purpura

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed written informed consent.
Subject is ≥18 years old.
Diagnosis of HBV-infection duration for at least 6 months prior to the study and have a platelet count of <30 ×109/L on Day 1 (or within 48 hours prior to dosing on Day 1).
Complete blood count results: white blood cells, absolute neutrophils count and hemoglobin are within the laboratory normal range, but abnormalities caused by HBV infection can be accepted.
Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study.

Exclusion Criteria:

Liver cirrhosis (LC) defined as any of the following:
1. Any symptom or sign typical of hepatic decompensation: including but not limited to ascites, splenomegaly, dilation of periumbilical collateral veins, hepatic encephalopathy
2. Child-Pugh class B to C Biopsies are not required either for confirmation or for exclusion of LC, considering the high bleeding risk in these patients.
Positive serology for HIV, hepatitis C virus (HCV), and/or hepatitis D virus (HDV).
Pregnancy or lactation period.
History of alcohol/drug abuse or dependence within 12 months of the study.
History of thrombosis.
The serum chemistry results exceed the upper laboratory normal range by more than 20%; except AST, ALT, GGT, ALP of CTCAE grade 1.
Bone marrow examination conducted within 4 weeks prior to first dose reported an abnormal result, which in the opinion of the investigator makes the subject unsuitable for participation in the study.
Pre-existing cardiac disease, including congestive heart failure of New York Heart Association [NYHA] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT >450msec or QTc > 480 for patients with a Bundle Branch Block.
Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks prior to the study start and until the end of the study.
Non-compliant patient
Reluctance to take effective contraceptive measures during the trial
History of solid organ or bone marrow transplant.

Sites / Locations

Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eltrombopag

Arm Description

58 enrolled patients are picked up to take eltrombopag at the indicated dose.

Outcomes

Primary Outcome Measures

Proportion of subjects with a platelet count ≥ 50×109/L at Day 43

The proportion of subjects with a platelet count ≥ 50×109/L at Day 43 after the first 6 weeks of Eltrombopag treatment (Stage 1)

Secondary Outcome Measures

Response rate of treatment

Response rate including: a) the proportion of subjects achieving platelet counts ≥ 50×109/L at least once during the first 6 weeks (stage 1); b) the proportion of subjects whose platelet counts ≥ 30×109/L and at least two times of baseline platelet count at least once during the treatment.

Bleeding in two stages

according to the WHO bleeding grades to estimate the incidence and severity of bleeding symptoms during the treatment.

The duration time with Platelet count ≥ 50×109/L

Total duration of time a subject had a platelet count ≥ 50×109/L during treatment.

Full Information

NCT ID

NCT03664518

First Posted

August 26, 2018

Last Updated

August 8, 2023

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Collaborators

Novartis, Qilu Hospital of Shandong University, The Second Affiliated Hospital of Kunming Medical University, Tianjin First Central Hospital, Tianjin Medical University Second Hospital, Henan Cancer Hospital, The Second Hospital of Hebei Medical University, North China University of Technology Affiliated Hospital, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of University of Science and Technology of China, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Second Affiliated Hospital of Guangzhou Medical University

1. Study Identification

Unique Protocol Identification Number

NCT03664518

Brief Title

to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia With Chronic HBV Infection

Official Title

A Multicenter Single-arm Study to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia in Chinese Patients With Chronic HBV Infection

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

December 4, 2018 (Actual)

Primary Completion Date

June 30, 2022 (Actual)

Study Completion Date

September 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Primary Objective: To evaluate the efficacy of 6-week Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection. Secondary Objective: To evaluate the efficacy and safety of 6-week and 22-week Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection.

Detailed Description

This is a single-arm phase II study to evaluate the efficacy and safety of Eltrombopag to treat immune thrombocytopenia with chronic hepatitis B virus infection. This study includes two stages. In Stage 1 (Week 1 to Week 6), the short-term efficacy, safety and tolerability of Eltrombopag is evaluated. At the end of Stage 1, the subjects who can benefit from Eltrombopag treatment (platelet count ≥30×109/L at least once and a 2-fold increase from baseline platelet count without rescue therapy, with no bleeding) can enter a 16-week prolonged stage (Stage 2) to evaluate longer-term efficacy and safety. The starting dose of Eltrombopag is 25 mg once daily, and the dose may be increased by 25 mg once daily according to protocol if the desired platelet response (>50×109/L) is not achieved. The daily dose should not exceed 75 mg. In Stage 1, weekly visits are required during the first 6 weeks of the study. In Stage 2, platelet counts will be obtained weekly during dose adjustment and every 4 weeks following establishment of a stable dose of Eltrombopag (stable dose is defined as the dose which remains unchanged for at least 2 weeks).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombocytopenia Purpura, Chronic HBV Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Eltrombopag

Arm Type

Experimental

Arm Description

58 enrolled patients are picked up to take eltrombopag at the indicated dose.

Intervention Type

Drug

Intervention Name(s)

Eltrombopag

Intervention Description

subjects will initiate treatment with 25 mg eltrombopag. Platelet counts is obtained weekly and dose adjustment should be done according to platelet counts. and maximum dose should not exceed 75 mg daily. Subjects whose platelet count between 50~150×109/L，the eltrombopag dose Maintain. platelet count between 150~250×109/L, need to reduce the dose of eltrombopag to the next lower dose or lower frequency. Subjects whose platelet count exceeds 250×109/L at any point during the treatment period, must have eltrombopag interrupted and increase the frequency of platelet monitoring to twice weekly, until platelet counts fall below 100×109/L.

Primary Outcome Measure Information:

Title

Proportion of subjects with a platelet count ≥ 50×109/L at Day 43

Description

The proportion of subjects with a platelet count ≥ 50×109/L at Day 43 after the first 6 weeks of Eltrombopag treatment (Stage 1)

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Response rate of treatment

Description

Time Frame

22 weeks

Title

Bleeding in two stages

Description

according to the WHO bleeding grades to estimate the incidence and severity of bleeding symptoms during the treatment.

Time Frame

22 weeks

Title

The duration time with Platelet count ≥ 50×109/L

Description

Total duration of time a subject had a platelet count ≥ 50×109/L during treatment.

Time Frame

22 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed written informed consent. Subject is ≥18 years old. Diagnosis of HBV-infection duration for at least 6 months prior to the study and have a platelet count of <30 ×109/L on Day 1 (or within 48 hours prior to dosing on Day 1). Complete blood count results: white blood cells, absolute neutrophils count and hemoglobin are within the laboratory normal range, but abnormalities caused by HBV infection can be accepted. Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study. Exclusion Criteria: Liver cirrhosis (LC) defined as any of the following: Any symptom or sign typical of hepatic decompensation: including but not limited to ascites, splenomegaly, dilation of periumbilical collateral veins, hepatic encephalopathy Child-Pugh class B to C Biopsies are not required either for confirmation or for exclusion of LC, considering the high bleeding risk in these patients. Positive serology for HIV, hepatitis C virus (HCV), and/or hepatitis D virus (HDV). Pregnancy or lactation period. History of alcohol/drug abuse or dependence within 12 months of the study. History of thrombosis. The serum chemistry results exceed the upper laboratory normal range by more than 20%; except AST, ALT, GGT, ALP of CTCAE grade 1. Bone marrow examination conducted within 4 weeks prior to first dose reported an abnormal result, which in the opinion of the investigator makes the subject unsuitable for participation in the study. Pre-existing cardiac disease, including congestive heart failure of New York Heart Association [NYHA] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT >450msec or QTc > 480 for patients with a Bundle Branch Block. Subject has consumed aspirin, aspirin-containing compounds, salicylates, anticoagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for >3 consecutive days within 2 weeks prior to the study start and until the end of the study. Non-compliant patient Reluctance to take effective contraceptive measures during the trial History of solid organ or bone marrow transplant.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

lei zhang, MD

Organizational Affiliation

Chinese Academy of Medical Science and Blood Disease Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.

IPD Sharing Time Frame

From 12 months 36 months after study completion.

IPD Sharing Access Criteria

Upon request to PI.

Citations:

PubMed Identifier

22273662

Citation

Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012 Mar 9;30(12):2212-9. doi: 10.1016/j.vaccine.2011.12.116. Epub 2012 Jan 24.

Results Reference

background

PubMed Identifier

23294591

Citation

Zhang Y, Zhang H, Elizabeth A, Liu XQ. Epidemiology of hepatitis B and associated liver diseases in china. Chin Med Sci J. 2013 Jan;27(4):243-8. doi: 10.1016/s1001-9294(13)60009-7.

Results Reference

background

PubMed Identifier

853132

Citation

Toghill PJ, Green S, Ferguson F. Platelet dynamics in chronic liver disease with special reference to the role of the spleen. J Clin Pathol. 1977 Apr;30(4):367-71. doi: 10.1136/jcp.30.4.367.

Results Reference

background

PubMed Identifier

15763973

Citation

Aref S, Mabed M, Selim T, Goda T, Khafagy N. Thrombopoietin (TPO) levels in hepatic patients with thrombocytopenia. Hematology. 2004 Oct-Dec;9(5-6):351-6. doi: 10.1080/10245330400010620.

Results Reference

background

PubMed Identifier

18433919

Citation

Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008 Jun;48(6):1000-7. doi: 10.1016/j.jhep.2008.03.009. Epub 2008 Mar 31.

Results Reference

background

PubMed Identifier

18607406

Citation

Bussel JB, Marks KM. How effective is eltrombopag for the treatment of thrombocytopenia in patients with HCV infection? Nat Clin Pract Gastroenterol Hepatol. 2008 Aug;5(8):424-5. doi: 10.1038/ncpgasthep1185. Epub 2008 Jul 8. No abstract available.

Results Reference

background

PubMed Identifier

27734464

Citation

Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. doi: 10.1111/bjh.14380. Epub 2016 Oct 13.

Results Reference

result

PubMed Identifier

18046028

Citation

Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275.

Results Reference

result

PubMed Identifier

23452139

Citation

Giannini EG, Afdhal NH. Eltrombopag in patients with chronic liver disease. Expert Opin Pharmacother. 2013 Apr;14(5):669-78. doi: 10.1517/14656566.2013.775249. Epub 2013 Mar 4.

Results Reference

result

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to Evaluate the Efficacy and Safety of Eltrombopag for Immune Thrombocytopenia With Chronic HBV Infection

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