Last updated: 11/07/2018 19:42:06
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: Randomised, placebo-controlled, multi-centre study to assess the efficacy and safety of eltrombopag in thrombocytopenic subjects with hepatitis C virus (HCV) infection who are otherwise eligible to initiate antiviral therapy (peginterferon alfa-2b plus ribavirin)
Trial description: The purpose of this study is to assess the ability of eltrombopag to maintain a platelet count sufficient to facilitate initiation of antiviral therapy, to minimise antiviral therapy dose reductions and to avoid permanent discontinuation of antiviral therapy. The clinical benefit of eltrombopag will be measured by the proportion of subjects who are able to achieve a Sustained Virological Response (SVR).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with sustained virologic response (SVR) in the Double-blind (DB) Antiviral Treatment Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Secondary outcomes:
Number of participants whose platelet count increased from a baseline count of <75 Gi/L to a count greater than or equal to (>=) 100 giga (10^9) cells per liter (Gi/L) during the Open-label (OL) Pre-Antiviral Treatment Phase
Timeframe: From Baseline up to Week 9 in the OL Phase
Number of participants receiving the indicated doses of eltrombopag in the OL Phase who initiated antiviral therapy (peginterferon alfa-2a and ribavirin) in the DB Phase
Timeframe: From Baseline up to Week 9 in the OL Phase
Median platelet count at the indicated time points during the OL Phase
Timeframe: OL Phase: Baseline; Day 1; Weeks 1, 2, 3, 4, 5, 6, 7, 8, and 9; Antiviral Baseline (up to Week 10); End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 62); 12-week FU (up to Week 70); and 24-week FU (up to Week 82)
Median platelet count at the indicated time points during the DB Phase
Timeframe: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Number of participants in the indicated categories for minimum platelet count with antiviral therapy
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with Rapid Virological Response (RVR) and Extended RVR (eRVR) during the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with Early Virological Response (EVR) and Complete EVR (cEVR) during the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with End of Treatment Response (ETR) and Sustained Virological Response at Week 12 of follow-up (SVR12) during the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants in the indicated categories for antiviral therapy dose reductions in the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Time to first dose reduction of peginterferon alfa-2a and ribavirin therapy in the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with the indicated levels of peginterferon dose reductions in the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants who prematurely discontinued antiviral therapy in the DB Phase
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants categorized as responders (R) and non-responders (NR) for SVR and RVR to antiviral therapy in the indicated variants of Interleukin 28B (IL28B) (or interferon, lambda 3)
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with the indicated shift from Baseline (BL) in severity grades for clinical chemistry parameters (calcium, glucose [glu.], potassium [pot.], and sodium [sod.]), per Division of Acquired Immunodeficiency Syndrome (DAIDS)
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants with the indicated shifts from BL in severity grades for for hematology parameters (hemoglobin, lymphocytes [lym.], total neutrophils [tot neu.], and white blood cells [WBC]), per DAIDS
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants in the indicated categories for cataract event during the DB Phase, per Clinical Events Committee (CEC) adjudication
Timeframe: From Baseline up to Week 48 or Week 72 (for participants with Genotype 2/3) or up to Week 72 (for participants with Non-Genotype 2/3)
Number of participants assessed as normal and abnormal (clinically significant [CS] and not clinically significant [NCS]) for 12-lead electrocardiogram (ECG) at the indicated time points during the DB Phase
Timeframe: DB Phase: Antiviral BL (up to Week 10); End of Treatment (up to Week 52); and 24-week FU (up to Week 72)
Number of participants with CS and NCS change from Baseline for 12-lead ECG at the indicated time points during the DB Phase
Timeframe: End of Treatment (up to Week 52); and 24-week FU (up to Week 72)
Mean change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the indicated time points during the DB Phase
Timeframe: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Mean change from Baseline in heart rate at the indicated time points during the DB Phase
Timeframe: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Mean change from Baseline in weight at the indicated time points during the DB Phase
Timeframe: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Mean change from Baseline in Body Mass Index (BMI) at the indicated time points during the DB Phase
Timeframe: DB Phase: Baseline; Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44; End of Treatment (up to Week 48); 4-week Follow-up (FU) (up to Week 52); 12-week FU (up to Week 60); and 24-week FU (up to Week 72)
Interventions:
Drug: eltrombopag
Drug: placebo
Enrollment:
759
Observational study model:
Not applicable
Primary completion date:
2011-23-08
Time perspective:
Not applicable
Clinical publications:
Afdhal NH, Dusheiko GM, Giannini EG, Chen P-J, Han K-H, Mohsin A, Rodriguez-Torres M, Rugina S, Bakulin I, Lawitz E, Shiffman ML, Tayyab G-U-N, Poordad F, Mostafa Kamel Y, Brainsky A, Geib J, Vasey SY, Patwardhan R, Campbell FM, Theodore D.Eltrombopag Increases Platelet Numbers in Thrombocytopenic Patients With HCV Infection and Cirrhosis, Allowing for Effective Antiviral Therapy.Gastroenterology.2014;146(2):442-452
Afdhal, Dusheiko, Giannini, Chen, Han, Mohsin, Rodriguez-Torres, Rugina, Bakulin, Lawitz, Shiffman, Tayyab, Poordad, Mostafa Kamel, Brainsky, Geib, Vasey, Patwardhan, Campbell, Theodore.Eltrombopag Increases Platelet Numbers in Thrombocytopenic Patients with HCV Infection and Cirrhosis, Allowing for Effective Antiviral Therapy.Gastroenterology.2014;146(2):442-452
Medical condition
Hepatitis C, Chronic
Product
eltrombopag
Collaborators
Not applicable
Study date(s)
October 2007 to August 2011
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Male and female subjects, >18 years
- Evidence of chronic hepatitis C virus (HCV) infection
- Non-responders to previous treatment with pegIFN and ribavirin who failed to achieve a sustained virologic response (SVR) for reasons other than thrombocytopenia, despite an optimal course (dose and duration) of combination therapy with pegIFN and ribavirin
- Decompensated liver disease, e.g. Child-Pugh score >6 or history of ascites or hepatic encephalopathy or current evidence of ascites
Inclusion and exclusion criteria
Inclusion criteria:
- Male and female subjects, >18 years Evidence of chronic hepatitis C virus (HCV) infection Subjects who are appropriate candidates for peginterferon (pegIFN) and ribavirin antiviral therapy A platelet count of <75,000/mcL Haemoglobin >11.0g/dL for men or >10.0g/dL for women Absolute neutrophil count (ANC) >750/mm3 and no history of infections associated with neutropenia Creatinine clearance >50mL/minute All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment end Subject is able to understand, consent and comply with protocol requirements and instructions and is likely to complete the study as planned
Exclusion criteria:
- Non-responders to previous treatment with pegIFN and ribavirin who failed to achieve a sustained virologic response (SVR) for reasons other than thrombocytopenia, despite an optimal course (dose and duration) of combination therapy with pegIFN and ribavirin Decompensated liver disease, e.g. Child-Pugh score >6 or history of ascites or hepatic encephalopathy or current evidence of ascites Known hypersensitivity, intolerance or allergy to interferon (IFN), ribavirin, eltrombopag or any of their ingredients Serious cardiac, cerebrovascular, or pulmonary disease that would preclude treatment with pegIFN and ribavirin Subjects with a history of any one of the following: Suicide attempt or hospitalisation for depression in the past 5 years Any current severe or poorly controlled psychiatric disorder The following subjects are eligible for study participation, but must be assessed and followed (if recommended) by a mental health professional:
- Subjects who have had a severe or poorly controlled psychiatric disorder more than 6 months ago but less than 5 years ago
- Seizure disorder that has not been well controlled History of clinically significant bleeding from oesophageal or gastric varices Subjects with haemoglobinopathies, e.g. sickle cell anaemia, thalassemia major Any prior history of arterial or venous thrombosis AND two or more of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc), hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer Pre-existing cardiac disease (New York Heart Association (NYHA) Grade III/IV), or arrhythmias known to involve the risk of thromboembolic events, or corrected QT interval (QTc) >450 msec Evidence of hepatocellular carcinoma Laboratory evidence of infection with human immunodeficiency virus (HIV) or active Hepatitis B Virus (HBV) infection Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin Therapy with any anti-neoplastic or immuno-modulatory treatment <6 months prior to the first dose of eltrombopag. Subjects who have had a malignancy diagnosed and/or treated within the past 5 years, except for subjects with localised basal or squamous cell carcinoma treated by local excision or subjects with malignancies who have been adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival Pregnant or nursing women Males with a female partner who is pregnant History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation programme) Treatment with an investigational drug or IFN within 30 days or 5 half-lives (whichever is longer) of the screening visit History of platelet clumping that prevents reliable measurement of platelet counts History of major organ transplantation with an existing functional graft Thyroid dysfunction not adequately controlled Subjects planning to have cataract surgery Evidence of portal vein thrombosis on abdominal imaging within 3 months of the baseline visit
Trial location(s)
Location
GSK Investigational Site
Siegen, Nordrhein-Westfalen, Germany, 57072
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
Ponce, Puerto Rico, Puerto Rico, 00717
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Bradenton, Florida, United States, 34209
Status
Study Complete
Location
GSK Investigational Site
Victoria, British Columbia, Canada, V8V 3P9
Status
Study Complete
Location
GSK Investigational Site
Campinas, São Paulo, Brazil, 13083-888
Status
Study Complete
Location
GSK Investigational Site
Arcadia, California, United States, 91007
Status
Terminated/Withdrawn
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Morganton, North Carolina, United States, 28655
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Los Angeles, California, United States, 90017
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95817
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Chicago, Illinois, United States, 60612-3824
Status
Study Complete
Location
GSK Investigational Site
San Mateo, California, United States, 94403
Status
Study Complete
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Status
Study Complete
Location
GSK Investigational Site
New Haven, Connecticut, United States, 06510
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78215
Status
Study Complete
Location
GSK Investigational Site
Manhasset, New York, United States, 11030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02215
Status
Study Complete
Location
GSK Investigational Site
Leverkusen, Nordrhein-Westfalen, Germany, 51375
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lynwood, California, United States, 90262
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Regensburg, Bayern, Germany, 93049
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Deggendorf, Bayern, Germany, 94469
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Shebeen El-Kom, Menoufeya, Egypt, 35111
Status
Study Complete
Location
GSK Investigational Site
New Orleans, Louisiana, United States, 70112
Status
Study Complete
Location
GSK Investigational Site
Anaheim, California, United States, 92801
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39120
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Los Angeles, California, United States, 90048
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44787
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48143
Status
Study Complete
Location
GSK Investigational Site
San Giovanni Rotondo (FG), Puglia, Italy, 71013
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20010
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lexington, Kentucky, United States, 40536
Status
Study Complete
Location
GSK Investigational Site
Worcester, Massachusetts, United States, 01655
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Burlington, Massachusetts, United States, 01805
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32207
Status
Terminated/Withdrawn
Location
GSK Investigational Site
San Diego, California, United States, 92123
Status
Study Complete
Location
GSK Investigational Site
Hershey, Pennsylvania, United States, 17033-0850
Status
Study Complete
Location
GSK Investigational Site
Aachen, Nordrhein-Westfalen, Germany, 52074
Status
Study Complete
Location
GSK Investigational Site
Washington, District of Columbia, United States, 20307
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 12
Status
Study Complete
Location
GSK Investigational Site
Aurora, Colorado, United States, 80045
Status
Study Complete
Location
GSK Investigational Site
Fitzroy, Victoria, Australia, 3065
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jackson, Mississippi, United States, 39202
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kinston, North Carolina, United States, 28501
Status
Study Complete
Location
GSK Investigational Site
Goettingen, Niedersachsen, Germany, 37075
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23249
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10016
Status
Study Complete
Location
GSK Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Camperdown, New South Wales, Australia, 2050
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Honolulu, Hawaii, United States, 96817
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97239
Status
Study Complete
Location
GSK Investigational Site
La Jolla, California, United States, 92037
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294-0005
Status
Study Complete
Location
GSK Investigational Site
São Paulo, São Paulo, Brazil, 04023900
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27710
Status
Study Complete
Location
GSK Investigational Site
Asheville, North Carolina, United States, 28801
Status
Study Complete
Location
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Halle, Sachsen-Anhalt, Germany, 06120
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Winnipeg, Manitoba, Canada, R3E 3P4
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Herne, Nordrhein-Westfalen, Germany, 44623
Status
Study Complete
Location
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48202
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Location
GSK Investigational Site
Rotenburg (Wuemme), Niedersachsen, Germany, 27356
Status
Study Complete
Location
GSK Investigational Site
Syracuse, New York, United States, 13210
Status
Study Complete
Location
GSK Investigational Site
Rochester, New York, United States, 14642
Status
Study Complete
Location
GSK Investigational Site
San Juan, Puerto Rico, Puerto Rico, 00927
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63104
Status
Study Complete
Location
GSK Investigational Site
Oberhausen, Nordrhein-Westfalen, Germany, 46045
Status
Study Complete
Location
GSK Investigational Site
San Clemente, California, United States, 92673
Status
Study Complete
Location
GSK Investigational Site
Dortmund, Nordrhein-Westfalen, Germany, 44263
Status
Study Complete
Location
GSK Investigational Site
Tulsa, Oklahoma, United States, 74104
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Mountain Home, Tennessee, United States, 37684
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Seattle, Washington, United States, 98111
Status
Study Complete
Location
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53127
Status
Study Complete
Location
GSK Investigational Site
Germantown, Tennessee, United States, 38138
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10021
Status
Study Complete
Location
GSK Investigational Site
Galveston, Texas, United States, 77555-0435
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Garran, Australian Capital Territory, Australia, 2606
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37212
Status
Study Complete
Location
GSK Investigational Site
Hof/Saale, Bayern, Germany, 95028
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Study Complete
Location
GSK Investigational Site
Beeskow, Brandenburg, Germany, 15848
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70197
Status
Study Complete
Location
GSK Investigational Site
Catanzaro, Calabria, Italy, 88100
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37205
Status
Study Complete
Location
GSK Investigational Site
Charlottesville, Virginia, United States, 22908
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
No longer a GSK study
Actual primary completion date
2011-23-08
Actual study completion date
2011-23-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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