SB497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adults With Thrombocytopenia Due To Hepatitis C

Study Overview
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Brief Summary
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SB497115 is an oral agent which activates the thrombopoietin receptor and increases platelet counts in healthy volunteers. This study is examining several different doses of SB497115 as a treatment for patients with chronic hepatitis C-related thrombocytopenia who are potential candidates for antiviral treatment with pegylated interferon and ribavirin. The study will be conducted in two phases, Parts 1 and 2. In Part 1, study subjects will be randomized to 4 weeks of SB-497115-GR or placebo administered daily without antiviral therapy. Subjects who successfully complete Part 1 (platelet count 70,000/µL for Pegasys and platelet count 100,000/µL for PEG-Intron) will then proceed to Part 2. In Part 2, subjects will receive an additional 8 weeks of SB-497115-GR or placebo administered daily with antiviral therapy.

Detailed Description
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A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre, Dose-Ranging, Parallel Group, Phase II Study to Assess Efficacy, Safety/Tolerability, and Pharmacokinetics of a Thrombopoietin Receptor Agonist, SB-497115-GR, when Administered as 30, 50, and 75 mg Once Daily for 12 weeks in Subjects with Chronic Hepatitis C-Related Thrombocytopenia who are Potential Candidates for Antiviral Treatment with Pegylated Interferon and Ribavirin.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Multi-Centre, Dose-Ranging, Parallel Group, Phase II Study to Assess Efficacy, Safety/Tolerability, and Pharmacokinetics of a Thrombopoietin Receptor Agonist, SB-497115-GR, When Administered as 30, 50, and 75 mg Once Daily for 12 Weeks in Subjects With

Conditions
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Hepatitis C, Chronic, Hepatitis C, Thrombocytopenia

Intervention / Treatment
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* Drug: SB497115
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic low platelet count between 20,000 and <70,000/µL. Prior liver biopsy indicating chronic hepatitis within the previous 5 years or radiographic evidence of cirrhosis and / or endoscopic evidence of non-bleeding esophageal or gastric varices. Exclusion criteria: History of heart attack or abnormal heart function. History of thrombosis within 1 year. History of alcohol or drug abuse or dependence within 1 year. Use of aspirin, aspirin-containing compounds, salicylates, antacids. History of HIV infection or active infection with Hepatitis B or C. Females who are pregnant. Patients using non-steroidal anti-inflammatory drugs during the study and within 3 weeks prior to starting the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm B<br>SB-497115-GR 30mg administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy. | Drug: SB497115<br>* Approximately 160 subjects will be randomized equally to one of four treatment groups of approximately 40 subjects (A-D). Subjects will receive oral tablets of SB-497115-GR at 30mg, 50 mg, 75 mg or placebo administered once daily for a total of 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.<br>|
| Active Comparator: Arm C<br>SB-497115-GR 50mg administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy. | Drug: SB497115<br>* Approximately 160 subjects will be randomized equally to one of four treatment groups of approximately 40 subjects (A-D). Subjects will receive oral tablets of SB-497115-GR at 30mg, 50 mg, 75 mg or placebo administered once daily for a total of 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.<br>|
| Active Comparator: Arm D<br>SB-497115-GR 75mg administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy. | Drug: SB497115<br>* Approximately 160 subjects will be randomized equally to one of four treatment groups of approximately 40 subjects (A-D). Subjects will receive oral tablets of SB-497115-GR at 30mg, 50 mg, 75 mg or placebo administered once daily for a total of 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.<br>|
| Placebo Comparator: Arm A<br>Placebo administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy. | Other: Placebo<br>* Placebo administered orally daily for 12 weeks beginning 4 weeks prior to initiating 8 weeks of antiviral therapy and for 8 weeks during weekly antiviral therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response, assessed by the proportion of subjects with a shift from baseline platelet count (20, 000 to <70,000µL) to =100,000/µL after 4 weeks of study treatment. |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean increase in platelet counts and markers of thrombopoiesis. Safety and tolerability, population PK, pharmacodynamics. Effect of antiviral outcome measures during and after therapy. |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombopoietin, platelets, Hepatitis C-related thrombocytopenia, Hepatitis C