ENABLE 1 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C related Liver DiseasE) Randomised, placebo-controlled, multi-centre study to assess the efficacy and safety of eltrombopag in thrombocytopenic subjects with hepatitis C virus (HCV) infection who are otherwise eligible to initiate antiviral therapy (peginterferon alfa-2a plus ribavirin) - ENABLE 1

INTERVENTION:

Product Name: Eltrombopag Product Code: SB‐497115 Pharmaceutical Form: Tablet INN or Proposed

INN:

Eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ INN or Proposed

INN:

Eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ INN or Proposed

INN:

Eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 75‐ INN or Proposed

INN:

Eltrombopag CAS Number: CASRN496775 Current Sponsor code: SB‐497115 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use

CONDITION:

Thrombocytopenic subjects with hepatitis C viral infection ; MedDRA version: 9.1 Level: LLT Classification code 10019744 Term: Hepatitis

C PRIMARY OUTCOME:

Main Objective: To evaluate the effect of eltrombopag treatment on SVR in thrombocytopenic subjects (platelets <75,000/microL) with hepatitis C virus (HCV) infection Primary end point(s): Sustained virological response (SVR) rate defined as percentage of subjects with non‐detectable HCV‐RNA at 24 weeks post‐completion of the planned treatment period (i.e., Week 48 for genotype 2/3 or Week 72 for non‐genotype 2/3). Secondary Objective: 1. To evaluate ability of eltrombopag to enable initiation of antiviral therapy in thrombocytopenic subjects with HCV infection; 2. To evaluate ability of eltrombopag to maintain antiviral therapy in thrombocytopenic subjects with HCV infection; 3. To evaluate safety/tolerability of eltrombopag when administered once daily in thrombocytopenic subjects with HCV infection; 4. To evaluate effect of eltrombopag on platelet counts in thrombocytopenic subjects with HCV infection; 5. To describe PK of eltrombopag and explore its relationship with relevant safety & efficacy endpoints; 6. To evaluate effects of eltrombopag treatment on antiviral treatment outcome measures (RVR, EVR and ETR in thrombocytopenic subjects with HCV infection; 7. To evaluate impact of eltrombopag on subject reported symptoms and HRQo

L INCLUSION CRITERIA:

1. Male and female subjects, =18 years of age. 2. Evidence of chronic HCV infection (quantifiable HCV RNA). 3. Subjects who, in the opinion of the investigator, are appropriate candidates for Peginterferon alfa‐2a and ribavirin combination antiviral therapy. 4. A baseline platelet count <75,000/microL 5. Haemoglobin concentration >11.0g/dL for men or at least 10.0g/dL for women 6. Absolute neutrophil count (ANC) at least 750/mm3 and no history of infections associated with neutropenia 7. Alpha‐fetoprotein up to 200ng/mL at screening. 8. Creatinine clearance at least 50mL/minute. 9. All fertile males must use two forms of effective contraception during treatment and during the 24 weeks after treatment end. 10. A female is eligible to enter and participate in the study if she is of: • Non‐childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who: • Has had a hysterectomy •