Back to resultsClinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390 (ENABLE-ALL)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eltrombopag
Antiviral therapy
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C focused on measuring Peginterferon, Platelets, Ribavirin, Hepatitis C-related thrombocytopenia, Thrombocytopenia, Hepatitis C, Thrombopoietin
Eligibility Criteria
Inclusion Criteria:
- Prior participation in protocol TPL103922 or TPL108390 and completed the Week 24 Follow Up Visit in TPL103922 or TPL108390
- Male or female ≥18 years old
- Evidence of chronic HCV infection
- While participating in TPL103922 or TPL108390, discontinued from study drug due to thrombocytopenia
- Appropriate candidate for antiviral therapy with pegylated interferon plus ribavirin
- Platelet count <75,000
- Fertile males and females must use two forms of effective contraception during treatment and for 24 weeks after treatment
- Ability to understand and comply with the protocol requirements and instructions
- Ability to provide written informed consent
Exclusion Criteria:
- Decompensated liver disease
- Known hypersensitivity, intolerance, or allergy to interferon, ribavirin, eltrombopag, or their ingredients
- History of clinically significant bleeding from oesophageal or gastric varices
- History of arterial or venous thrombosis and two or more of the following risk factors: hereditary thrombophilic disorders; hormone replacement therapy; systemic contraception (containing estrogen); smoking; diabetes; hypercholesterolemia; medication for hypertension or cancer
- Pre-existing cardiac disease (congestive heart failure Grade III/IV) or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
- Evidence of hepatocellular carcinoma
- HIV or Hepatitis B infection
- Therapy with anti-neoplastic or immunomodulatory treatment within six months prior to eltrombopag therapy
- Malignancy diagnosed or treated within the past five years. Except for localized basal or squamous cell carcinoma treated by local excision or malignancies that were adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival.
- Pregnant or nursing women
- Men with a female partner who is pregnant
- History of alcohol/drug abuse or dependence within six months of the study start unless participating in a controlled rehabilitation programme.
- Treatment with an investigational drug or interferon within 30 days or 5 half-lives (whichever is longer) of the screening visit
- History or platelet clumping that prevents reliable measurement of platelet counts
- Evidence of portal vein thrombosis within three months of baseline visit
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-label eltrombopag
Arm Description
Open-label eltrombopag with dose titrations to support adequate platelet counts.
Outcomes
Primary Outcome Measures
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Number of Participants With Any AE and Any SAE in Part 2
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Number of Participants With the Indicated Worst-case Division of Acquired Immune Deficiency Syndrome (DAIDS) Grade Increases From Screening for the Indicated Clinical Chemistry Parameters During Part 1
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Clinical Chemistry Parameter During Part 2
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1
Blood samples were collected for the measurement of hematology parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2
Blood samples were collected for the measurement of hematology chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2
Visual acuity (VA) is defined as acuteness or clearness of vision.
Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Secondary Outcome Measures
Platelet Counts at the Indicated Time Points
Blood samples were collected for the measurement of platelet count. For each participant, the duration of Part 1 treatment varies between 2 and 9 weeks.
Number of Particpants Who Initiated Antiviral Therapy
The number of participants who completed the Pre-antiviral Phase (Part 1) and proceeded to the Antiviral Phase (Part 2) are summarized.
Number of Participants Achieving Antiviral Treatment Milestones of Sustained Virological Response (SVR), Rapid Virological Response (RVR), Early Virological Response (EVR), and End of Treatment Response (ETR)
SVR is defined as non-detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of the planned treatment period (i.e., Week 48 or 72 for genotype 2/3 or Week 72 for non-genotype 2/3). RVR is defined as undetectable HCV RNA after 4 weeks of antiviral treatment. EVR is defined as clinically significant reduction in HCV RNA (>=2 log10 drop or undetectable) after 12 weeks of antiviral treatment. ETR is defined as undetectable HCV RNA at the end of antiviral treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00996216
Brief Title
Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390
Acronym
ENABLE-ALL
Official Title
An Open-label, Multi-centre Rollover Study to Assess the Safety and Efficacy of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2a or Peginterferon Alfa-2b Plus Ribavirin)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to test the safety and tolerability of eltrombopag when used to increase and maintain platelet count. Platelet count to be maintained at a level sufficient to facilitate initiation of antiviral therapy, to minimize antiviral therapy dose reductions, and to avoid permanent discontinuation of antiviral therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
Peginterferon, Platelets, Ribavirin, Hepatitis C-related thrombocytopenia, Thrombocytopenia, Hepatitis C, Thrombopoietin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open-label eltrombopag
Arm Type
Experimental
Arm Description
Open-label eltrombopag with dose titrations to support adequate platelet counts.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Other Intervention Name(s)
Promacta
Intervention Description
Eltrombopag starting at 25 mg dose and titrated in Part 1 of study to 50, 75, 100 mg. Platelet count must reach sufficient level to allow initiation of antiviral therapy. Eltrombopag dose may be adjusted during antiviral treatment phase of study to maintain platelet count to continue antiviral therapy without adjustment to antiviral dose.
Intervention Type
Drug
Intervention Name(s)
Antiviral therapy
Intervention Description
Combination of either peginterferon alfa-2a or alfa-2b with ribavirin at investigator's discretion.
Primary Outcome Measure Information:
Title
Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame
From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
Title
Number of Participants With Any AE and Any SAE in Part 2
Description
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame
From the date of initiation of antiviral therapy (Antiviral Baseline Visit [between Study Day 14 and Study Day 65]) to the completion of the follow-up period (up to Week 96/WD)
Title
Number of Participants With the Indicated Worst-case Division of Acquired Immune Deficiency Syndrome (DAIDS) Grade Increases From Screening for the Indicated Clinical Chemistry Parameters During Part 1
Description
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Time Frame
From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
Title
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Clinical Chemistry Parameter During Part 2
Description
Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Time Frame
From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)
Title
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1
Description
Blood samples were collected for the measurement of hematology parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Time Frame
From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
Title
Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2
Description
Blood samples were collected for the measurement of hematology chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.
Time Frame
From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD)
Title
Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2
Description
Visual acuity (VA) is defined as acuteness or clearness of vision.
Time Frame
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
Title
Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2
Description
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Time Frame
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
Title
Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2
Description
LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.
Time Frame
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
Secondary Outcome Measure Information:
Title
Platelet Counts at the Indicated Time Points
Description
Blood samples were collected for the measurement of platelet count. For each participant, the duration of Part 1 treatment varies between 2 and 9 weeks.
Time Frame
From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
Title
Number of Particpants Who Initiated Antiviral Therapy
Description
The number of participants who completed the Pre-antiviral Phase (Part 1) and proceeded to the Antiviral Phase (Part 2) are summarized.
Time Frame
From the start of the investigational product up to 9 weeks (median of 21 days)
Title
Number of Participants Achieving Antiviral Treatment Milestones of Sustained Virological Response (SVR), Rapid Virological Response (RVR), Early Virological Response (EVR), and End of Treatment Response (ETR)
Description
SVR is defined as non-detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of the planned treatment period (i.e., Week 48 or 72 for genotype 2/3 or Week 72 for non-genotype 2/3). RVR is defined as undetectable HCV RNA after 4 weeks of antiviral treatment. EVR is defined as clinically significant reduction in HCV RNA (>=2 log10 drop or undetectable) after 12 weeks of antiviral treatment. ETR is defined as undetectable HCV RNA at the end of antiviral treatment.
Time Frame
From the start of investigational product in Part 2 up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Prior participation in protocol TPL103922 or TPL108390 and completed the Week 24 Follow Up Visit in TPL103922 or TPL108390
Male or female ≥18 years old
Evidence of chronic HCV infection
While participating in TPL103922 or TPL108390, discontinued from study drug due to thrombocytopenia
Appropriate candidate for antiviral therapy with pegylated interferon plus ribavirin
Platelet count <75,000
Fertile males and females must use two forms of effective contraception during treatment and for 24 weeks after treatment
Ability to understand and comply with the protocol requirements and instructions
Ability to provide written informed consent
Exclusion Criteria:
Decompensated liver disease
Known hypersensitivity, intolerance, or allergy to interferon, ribavirin, eltrombopag, or their ingredients
History of clinically significant bleeding from oesophageal or gastric varices
History of arterial or venous thrombosis and two or more of the following risk factors: hereditary thrombophilic disorders; hormone replacement therapy; systemic contraception (containing estrogen); smoking; diabetes; hypercholesterolemia; medication for hypertension or cancer
Pre-existing cardiac disease (congestive heart failure Grade III/IV) or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
Evidence of hepatocellular carcinoma
HIV or Hepatitis B infection
Therapy with anti-neoplastic or immunomodulatory treatment within six months prior to eltrombopag therapy
Malignancy diagnosed or treated within the past five years. Except for localized basal or squamous cell carcinoma treated by local excision or malignancies that were adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival.
Pregnant or nursing women
Men with a female partner who is pregnant
History of alcohol/drug abuse or dependence within six months of the study start unless participating in a controlled rehabilitation programme.
Treatment with an investigational drug or interferon within 30 days or 5 half-lives (whichever is longer) of the screening visit
History or platelet clumping that prevents reliable measurement of platelet counts
Evidence of portal vein thrombosis within three months of baseline visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
GSK Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
GSK Investigational Site
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
GSK Investigational Site
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
GSK Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98111
Country
United States
Facility Name
GSK Investigational Site
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
GSK Investigational Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
GSK Investigational Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
Facility Name
GSK Investigational Site
City
Marseille Cedex 08
ZIP/Postal Code
13285
Country
France
Facility Name
GSK Investigational Site
City
Nice cedex 3
ZIP/Postal Code
06202
Country
France
Facility Name
GSK Investigational Site
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
GSK Investigational Site
City
Duesseldorf
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
40225
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
10969
Country
Germany
Facility Name
GSK Investigational Site
City
Athens
ZIP/Postal Code
10676
Country
Greece
Facility Name
GSK Investigational Site
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
GSK Investigational Site
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20157
Country
Italy
Facility Name
GSK Investigational Site
City
Lahore
ZIP/Postal Code
54600
Country
Pakistan
Facility Name
GSK Investigational Site
City
La Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28029
Country
Spain
Facility Name
GSK Investigational Site
City
Pontevedra
ZIP/Postal Code
36071
Country
Spain
Facility Name
GSK Investigational Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390
We'll reach out to this number within 24 hrs