Clinical trial NCT03664518: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thrombocytopenia Purpura
Chronic HBV Infection
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Novartis
name: Qilu Hospital of Shandong University
name: The Second Affiliated Hospital of Kunming Medical University
name: Tianjin First Central Hospital
name: Tianjin Medical University Second Hospital
name: Henan Cancer Hospital
name: The Second Hospital of Hebei Medical University
name: North China University of Technology Affiliated Hospital
name: The Affiliated Hospital of Qingdao University
name: The First Affiliated Hospital of University of Science and Technology of China
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Second Affiliated Hospital of Guangzhou Medical University
First posted: 2018-09-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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:

  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.

Primary outcomes:
measure: Proportion of subjects with a platelet count ≥ 50×109/L at Day 43
timeFrame: 6 weeks
Secondary outcomes:
measure: Response rate of treatment
timeFrame: 22 weeks
measure: Bleeding in two stages
timeFrame: 22 weeks
measure: The duration time with Platelet count ≥ 50×109/L
timeFrame: 22 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Ethics Committee of Blood disease hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Chinese Academy of Medical Science and Blood Disease Hospital
name: lei zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.
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