A Longitudinal 2-year Bone Marrow Study of Eltrombopag in Previously Treated Adults, With Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

NCT ID: NCT01098487

Last Updated: 2015-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-05-31

Brief Summary

A open-label, multi-center 2-year safety study to ascertain the baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP) and to evaluate the long-term effect of eltrombopag on bone marrow fibers. The study will also describe the long-term safety and tolerability of oral eltrombopag treatment in subjects with chronic ITP.

Detailed Description

This is a phase IV, open-label safety study, designed to determine baseline levels of bone marrow fibers in previously treated adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP)and to evaluate the long-term effect of eltrombopag on bone marrow reticulin and/or collagen fibers.

The duration of the screening period is up to 8 weeks. Eltrombopag will be administered for at least 2-years followed by a 4-week follow-up period. Bone marrow biopsies will be performed at screening, after 1-year and 2-years of eltrombopag treatment, and at early withdrawal of treatment. The screening bone marrow biopsy should be performed within 8 weeks of planned start of study medication and the bone marrow biopsy block must be available for central laboratory processing.

Conditions

Purpura, Thrombocytopaenic, Idiopathic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open Label

Oral eltrombopag once daily, starting dose 50 mg (or 25 mg for subjects of East Asian ancestry).

Group Type: EXPERIMENTAL

Eltrombopag olamine

Intervention Type: DRUG

Thrombopoietin receptor agonist

Interventions

Eltrombopag olamine

Thrombopoietin receptor agonist

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have signed and dated a written informed consent and be able to understand and comply with protocol requirements and instructions.
• Adults (≥18 years) diagnosed with chronic ITP according to the American Society for Hematology/British Committee for Standards in Hematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003; Provan, 2009]. In addition, a peripheral blood smear should support the diagnosis of ITP with no evidence of other disease causative of thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical examination should not suggest any disease, which may cause thrombocytopenia other than ITP.
• Subjects must be physically eligible for serial bone marrow biopsies and must have a bone marrow biopsy performed during screening, and be willing to remain on the study for at least 2 years with annual bone marrow biopsies.
• Subjects, who previously received eltrombopag or romiplostim, must have completed treatment with these therapies at least 6 months prior to the screening bone marrow biopsy.
• Subjects must have the following clinical chemistry values:
• ALT and AST < 2xULN;
• Bilirubin <1.5xULN (except for Gilbert's Syndrome);
• Subjects are practicing an acceptable method of contraception as specified in the protocol.
• In France, subjects will be eligible for inclusion in this study, only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• Subjects with any clinically relevant abnormality, other than ITP, or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another primary diagnosis (e.g., thrombocytopenia is secondary to another disease).
• Subjects with any concurrent malignant disease and/or a recent history of cancer treatment with systemic chemotherapy and/or radiotherapy.

Exception: Subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

• Subjects with any prior history of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), AND ≥ two of the following risk factors: hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, hypertension, cancer, hereditary thrombophilic disorders (e.g., Factor V Leiden, ATIII deficiency, etc), or any family history of arterial or venous thrombosis.
• Subjects with screening bone marrow fibers of either MF Grade 3 using European Consensus scale or Grade 4 using Bauermeister scale.
• Subjects with a QTc >450 msec or > 480 msec for subjects with Bundle Branch Block.
• Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotrophin (β-hCG) pregnancy test) at screening.
• Subjects treated with an investigational drug (other than a thrombopopoetin-receptor (TPO-R) agonist) within 30 days or five half-lives (whichever is longer) preceding the first dose of eltrombopag in the study. (For romiplostim or eltrombopag, see inclusion criterion #4).
• Subjects treated with any TPO-R agonist other than romiplostim or eltrombopag.
• Subjects with recent history of alcohol/drug abuse as determined by the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Caen, , France

GSK Investigational Site

Créteil, , France

GSK Investigational Site

Pessac, , France

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Shatin, New Territories, , Hong Kong

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Győr, , Hungary

GSK Investigational Site

Szeged, , Hungary

GSK Investigational Site

Ludhiana, , India

GSK Investigational Site

Pune, , India

GSK Investigational Site

Surat, , India

GSK Investigational Site

Vellore, , India

GSK Investigational Site

Bologna, Emilia-Romagna, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Padua, Veneto, Italy

GSK Investigational Site

Vicenza, Veneto, Italy

GSK Investigational Site

Karachi, , Pakistan

GSK Investigational Site

Lahore, , Pakistan

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Seongnam-si Gyeonggi-do, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

Countries

United States; Czechia; France; Germany; Hong Kong; Hungary; India; Italy; Pakistan; Russia; South Korea

References

Wong RS, Bakshi K, Brainsky A. Thrombophilia in patients with chronic immune thrombocytopenia. Scand J Clin Lab Invest. 2015 Jan;75(1):13-7. doi: 10.3109/00365513.2014.962597. Epub 2014 Oct 9.

Reference Type: DERIVED

PMID: 25296772 (View on PubMed)

Other Identifiers

112940

Identifier Type: -

Identifier Source: org_study_id