Clinical trial NCT00996216: Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Keywords: Peginterferon
Platelets
Ribavirin
Hepatitis C-related thrombocytopenia
Thrombocytopenia
Hepatitis C
Thrombopoietin
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1
timeFrame: From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
measure: Number of Participants With Any AE and Any SAE in Part 2
timeFrame: 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)
measure: 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
timeFrame: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
measure: 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
timeFrame: 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)
measure: Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1
timeFrame: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days)
measure: Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2
timeFrame: 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)
measure: Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2
timeFrame: 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)
measure: Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2
timeFrame: 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)
measure: Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2
timeFrame: 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 outcomes:
measure: Platelet Counts at the Indicated Time Points
timeFrame: 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)
measure: Number of Particpants Who Initiated Antiviral Therapy
timeFrame: From the start of the investigational product up to 9 weeks (median of 21 days)
measure: 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)
timeFrame: 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)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Camperdown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Marseille Cedex 08
country: France
facility: GSK Investigational Site
city: Nice cedex 3
country: France
facility: GSK Investigational Site
city: Pessac Cedex
country: France
facility: GSK Investigational Site
city: Freiburg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Duesseldorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: La Coruña
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pontevedra
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: