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

NCT01098487 | Completed Phase 4 Results

• 1 other identifier: 112940
• Study Type: interventional
• Target: 167
• Locations: 11 countries
• Sites: 34

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.

Conditions

Purpura, Thrombocytopaenic, Idiopathic

Keywords

Immune (idiopathic) thrombocytopenic purpura (ITP); bone marrow fibers; eltrombopag olamine; thrombopoietin receptor agonist

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Bone Marrow (BM) Fibers of MF Grade 0, 1, 2 and 3 on the European Consensus (EC) Scale at Baseline

  The evaluation of fibrosis was performed using BM biopsies in which the amount of fibrosis was assessed by the EC Grading Scale. This method distinguishes four degrees of fibrosis (myelofibrosis \[MF\]-0 to MF-3). MF Grade (G) 0 is scattered linear reticulin with no intersections (cross-overs) corresponding to normal BM; MF Grade 1 is loose network of reticulin with many intersections, especially in perivascular areas; MF Grade 2 is diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; MF Grade 3 is diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.

  Baseline

• Number of Participants With a Positive or Negative Collagen Level at Baseline

  The number of participants with a positive or negative collagen level was analyzed. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.

  Baseline

• Number of Participants With Indicated Grade Change From Baseline in the EC Grading Scale at 1 Year

  The change from baseline to on-treatment assessments of European Consensus (EC) scale was analyzed. On-treatment is defined as during the treatment period (including dose interruptions) and up to 14 days after the end of the treatment period. MF-0 is scattered linear reticulin with no intersections (cross-overs) corresponding to normal BM; MF-1 is loose network of reticulin with many intersections, especially in perivascular areas; MF-2 is diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; MF-3 is diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.

  Baseline and 1 year

• Number of Participants With Indicated Change From Baseline in the EC Grading Scale at 2 Years

  The change from baseline to on-treatment assessments of European Consensus (EC) scale was analyzed. On-treatment is defined as during the treatment period (including dose interruptions) and up to 14 days after the end of the treatment period. MF-0 is scattered linear reticulin with no intersections (cross-overs) corresponding to normal BM; MF-1 is loose network of reticulin with many intersections, especially in perivascular areas; MF-2 is diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; MF-3 is diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis. Baseline is defined as the most recent centrally-reviewed BM biopsy prior to first dose of eltrombopag in the study.

  Baseline and 2 years

• Number of Participants With a Positive or Negative Collagen Level at 1 Year

  The change from Baseline to on-treatment assessments of collagen level was analyzed. On-treatment is defined as during the treatment period (including dose interruptions) and up to 14 days after the end of the treatment period.

  1 year

• Number of Participants With a Positive or Negative Collagen Level at 2 Year

  The change from Baseline to on-treatment assessments of collagen level was analyzed. On-treatment is defined as during the treatment period (including dose interruptions) and up to 14 days after the end of the treatment period.

  2 years

Secondary Outcomes (3)

• Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline During the Study

  From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)

• Number of Participants With the Indicated Maximum Toxicity Grade for the Indicated Hematology Parameters at Any Time Post-Baseline During the Study

  From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)

• Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Started On-therapy + 1 Day, >1 to 30 Days Post Therapy and >30 Days Post Therapy

  From Week 1 up to Week 104 and up to 6 months follow-up (4 weeks for most participants) (up to approximately 2.5 years)

Study Arms (1)

Open Label

EXPERIMENTAL

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

Drug: Eltrombopag olamine

Interventions

Eltrombopag olamine DRUG

Thrombopoietin receptor agonist

Open Label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 any TPO-R agonist other than romiplostim or eltrombopag.
• Subjects with recent history of alcohol/drug abuse as determined by the investigator.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (34)

GSK Investigational Site

New York, New York, 10021, United States

Location

GSK Investigational Site

Hradec Králové, Czechia

Location

GSK Investigational Site

Olomouc, 775 20, Czechia

Location

GSK Investigational Site

Prague, 128 08, Czechia

Location

GSK Investigational Site

Caen, 14033, France

Location

GSK Investigational Site

Créteil, 94010, France

Location

GSK Investigational Site

Pessac, 33604, France

Location

GSK Investigational Site

Munich, Bavaria, 81241, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81377, Germany

Location

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40479, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 13353, Germany

Location

GSK Investigational Site

Shatin, New Territories, Hong Kong

Location

GSK Investigational Site

Debrecen, 4012, Hungary

Location

GSK Investigational Site

Győr, 9023, Hungary

Location

GSK Investigational Site

Szeged, 6720, Hungary

Location

GSK Investigational Site

Ludhiana, 141008, India

Location

GSK Investigational Site

Pune, 411004, India

Location

GSK Investigational Site

Surat, 395002, India

Location

GSK Investigational Site

Vellore, 632004, India

Location

GSK Investigational Site

Bologna, Emilia-Romagna, 40138, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20162, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Vicenza, Veneto, 36100, Italy

Location

GSK Investigational Site

Karachi, 75300, Pakistan

Location

GSK Investigational Site

Lahore, 54600, Pakistan

Location

GSK Investigational Site

Moscow, 125167, Russia

Location

GSK Investigational Site

Novosibirsk, 630087, Russia

Location

GSK Investigational Site

Saint Petersburg, 193024, Russia

Location

GSK Investigational Site

Seongnam-si Gyeonggi-do, 463-712, South Korea

Location

GSK Investigational Site

Seoul, 135-710, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

Related Publications (1)

• 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.

  PMID: 25296772 DERIVED

MeSH Terms

Conditions

Purpura; Purpura, Thrombocytopenic

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2010
• First Posted: April 2, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: March 12, 2015
• Results First Posted: March 12, 2015

Record last verified: 2015-02

Locations

HU (3); PA (2); CZ (3); HK (1); FR (3); IN (4); IT (5); RU (3); US (1); KR (3); DE (6)