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

NCT00996216 | Completed Phase 3 Results

• 1 other identifier: 108392
• Study Type: interventional
• Target: 27
• Locations: 9 countries
• Sites: 28

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.

Conditions

Hepatitis C

Keywords

Peginterferon; Platelets; Ribavirin; Hepatitis C-related thrombocytopenia; Thrombocytopenia; Hepatitis C; Thrombopoietin

Outcome Measures

Primary Outcomes (9)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

Secondary Outcomes (3)

• Platelet Counts at the Indicated Time Points

  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)

• Number of Particpants Who Initiated Antiviral Therapy

  From the start of the investigational product up to 9 weeks (median of 21 days)

• 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)

  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)

Study Arms (1)

Open-label eltrombopag

EXPERIMENTAL

Open-label eltrombopag with dose titrations to support adequate platelet counts.

Drug: Eltrombopag; Drug: Antiviral therapy

Interventions

Eltrombopag DRUG

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.

Also known as: Promacta

Open-label eltrombopag

Antiviral therapy DRUG

Combination of either peginterferon alfa-2a or alfa-2b with ribavirin at investigator's discretion.

Open-label eltrombopag

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (28)

GSK Investigational Site

San Diego, California, 92123, United States

Location

GSK Investigational Site

New Haven, Connecticut, 06520, United States

Location

GSK Investigational Site

Honolulu, Hawaii, 96817, United States

Location

GSK Investigational Site

Manhasset, New York, 11030, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37212, United States

Location

GSK Investigational Site

Seattle, Washington, 98111, United States

Location

GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

Location

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Herston, Queensland, 4029, Australia

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 3J4, Canada

Location

GSK Investigational Site

Marseille, 13285, France

Location

GSK Investigational Site

Nice, 06202, France

Location

GSK Investigational Site

Pessac, 33604, France

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10969, Germany

Location

GSK Investigational Site

Athens, 10676, Greece

Location

GSK Investigational Site

Bologna, Emilia-Romagna, 40138, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Lahore, 54600, Pakistan

Location

GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Madrid, 28029, Spain

Location

GSK Investigational Site

Pontevedra, 36071, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Hepatitis C; Thrombocytopenia; Jacobs syndrome

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

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 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 16, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: December 6, 2013
• Results First Posted: December 6, 2013

Record last verified: 2013-08

Locations

US (6); GR (1); FR (3); CA (2); PA (1); DE (5); AU (3); IT (3); ES (4)