Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390

Hepatitis C Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996216
• Other study ID #: 108392
• Status: Completed
• Phase: Phase 3
• First received: October 1, 2009
• Last updated: October 10, 2013
• Start date: September 2009
• Est. completion date: February 2013

Study information

• Verified date: August 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEurope: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• Eltrombopag
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.
• Antiviral therapy
Combination of either peginterferon alfa-2a or alfa-2b with ribavirin at investigator's discretion.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Camperdown	New South Wales
Australia	GSK Investigational Site	Herston	Queensland
Australia	GSK Investigational Site	Randwick	New South Wales
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Marseille Cedex 08
France	GSK Investigational Site	Nice cedex 3
France	GSK Investigational Site	Pessac Cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Greece	GSK Investigational Site	Athens
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Genova	Liguria
Italy	GSK Investigational Site	Milano	Lombardia
Pakistan	GSK Investigational Site	Lahore
Spain	GSK Investigational Site	La Coruña
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pontevedra
Spain	GSK Investigational Site	Valencia
United States	GSK Investigational Site	Honolulu	Hawaii
United States	GSK Investigational Site	Manhasset	New York
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Greece,  Italy,  Pakistan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days)	No
Primary	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.	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)	No
Primary	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.	From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)	No
Primary	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.	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)	No
Primary	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.	From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)	No
Primary	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.	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)	No
Primary	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.	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)	No
Primary	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.	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)	No
Primary	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.	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)	No
Secondary	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.	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)	No
Secondary	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.	From the start of the investigational product up to 9 weeks (median of 21 days)	No
Secondary	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.	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)	No