Phase 3 Efficacy and Safety Study of Peginterferon Lambda-1a and Ribavirin With Telaprevir

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Peginterferon Lambda-1a (Lambda) combined with Ribavirin (RBV) and Telaprevir (TVR) is effective in the treatment of chronic Hepatitis C (CHC) compared to Peginterferon Alfa-2a (alfa-2a) combined with RBV and Telaprevir.

Official Title
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A Phase 3 Blinded Randomized Study of Peginterferon Lambda-1a and Ribavirin Compared to Peginterferon Alfa-2a and Ribavirin, Each Administered With Telaprevir in Subjects With Genotype-1 Chronic Hepatitis C Who Are Treatment-naive or Relapsed on Prior Treatment With Peginterferon Alfa-2a and Ribavirin

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Biological: Peginterferon Lambda-1a
* Biological: Peginterferon Alfa-2a
* Drug: Ribavirin
* Drug: Telaprevir


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Chronic hepatitis C genotype 1. GT-1b Capped at 50 % of naïve subjects Naives to prior anti-HCV therapy [Interferon (IFN) and direct antiviral agent (DAA) based] Relapsers (defined as subjects who had undetectable HCV ribonucleic acid (RNA) on prior treatment regimen of alfa-2a/RBV and Hepatitis C Virus (HCV) RNA > 25IU/mL after discontinuation of treatment). Capped at 20% HCV RNA ≥ 100,000 IU/mL Subjects with compensated cirrhosis can be enrolled and will be capped at approximately 10% Seronegative for human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) Men or women, 18-70 years of age Exclusion Criteria: Chronic liver disease due to causes other than chronic HCV Current or past evidence of decompensation Conditions that preclude the use of Alfa/RBV/TVR per respective labels Diagnosed or suspected hepatocellular carcinoma
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 |
| --- | --- |
| Experimental: Part A: Peginterferon Lambda-1a + RBV + TVR<br> | Biological: Peginterferon Lambda-1a<br>* Syringes, subcutaneous (SC), 180μg, Once weekly, 24 or 48 weeks depending on response<br>Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 24 or 48 weeks depending on response<br>Drug: Telaprevir<br>* Tablets, Oral, 750 mg, three times a day, 12 weeks only<br>* Other names: Incivek;|
| Experimental: Part B (Arm 1): Peginterferon Lambda-1a + RBV + TVR<br> | Biological: Peginterferon Lambda-1a<br>* Syringes, subcutaneous (SC), 180μg, Once weekly, 24 or 48 weeks depending on response<br>Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 24 or 48 weeks depending on response<br>Drug: Telaprevir<br>* Tablets, Oral, 750 mg, three times a day, 12 weeks only<br>* Other names: Incivek;|
| Experimental: Part B (Arm 2): Peginterferon Lambda-2a + RBV + TVR<br> | Biological: Peginterferon Alfa-2a<br>* Syringes, SC, 180μg, Once weekly, 24 or 48 weeks depending on response<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 24 or 48 weeks depending on response<br>Drug: Telaprevir<br>* Tablets, Oral, 750 mg, three times a day, 12 weeks only<br>* Other names: Incivek;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) - Part A | eRVR was defined as Hepatitis C virus (HCV) RNA level below the lower limit of quantitation, target not detected at Weeks 4 and 12 of treatment. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (lower limit of quantitation =25 IU/mL; limit of detection   10 IU/mL). | Assessed at Week 4 and Week 12, week 12 reported | 
| Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) - Part B | SVR12 was defined as Hepatitis C virus (HCV) RNA level below lower limit of quantitation, target detected or not detected at Week 12 of post-treatment follow-up. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (lower limit of quantitation =25 IU/mL; limit of detection   10 IU/mL). | Follow-up Week 12 | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Drug Related AEs, Discontinuation Due to AEs, Dose Reductions and Death - Part A | An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a participant or clinical investigation participant administered an investigational (medicinal product. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or caused prolongation of existing hospitalization. | Day 1 of treatment up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) - Part A | SVR12 was defined as Hepatitis C virus (HCV) RNA level below lower limit of quantitation (LLOQ), target detected or not detected at Week 12 of post-treatment follow-up. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (LLOQ =25 IU/mL; limit of detection   10 IU/mL). | Follow-up Week 12 | 
| Percentage of Subjects With Sustained Virologic Response at Follow-Up Week 24 (SVR24) - Part A | SVR24 was defined as Hepatitis C virus (HCV) RNA level below lower limit of quantitation (LLOQ), target detected or not detected at Week 24 of post-treatment follow-up. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (LLOQ) =25 IU/mL; limit of detection   10 IU/mL). The analysis was performed using Modified Intent-to-Treat method defined as the proportions of participants meeting the response criteria in numerator and denominator based on all treated participants. The analysis was performed in all treated participants. | Follow up week 24 | 
| Percentage of Treatment-Naïve Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) - Part B | SVR12 was defined as Hepatitis C virus (HCV) RNA level below lower limit of quantitation, target detected or not detected at Week 12 of post-treatment follow-up. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (lower limit of quantitation =25 IU/mL; limit of detection   10 IU/mL). | Follow-up Week 12 | 
| Percentage of Participants With Treatment Emergent Cytopenic Abnormalities - Part B | Cytopenic abnormalities included anemia defined as hemoglobin <10 grams/decilitre; neutropenia defined as Absolute neutrophil count (ANC) <750 cubic millimetre (mm^3); thrombocytopenia defined as platelets <50,000 mm^3. | After Day 1 of treatment up to Week 48 | 
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) - Part B | eRVR was defined as Hepatitis C virus (HCV) RNA level below the lower limit of quantitation, target not detected at Weeks 4 and 12 of treatment. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (lower limit of quantitation =25 IU/mL; limit of detection   10 IU/mL). | Week 4 and Week 12 | 
| Percentage of Participants With On-Treatment Flu-Like Symptoms And Musculoskeletal Symptoms- Part B | Flu-like symptoms included pyrexia, chills, and pain. Musculoskeletal symptoms included arthralgia, myalgia, and back pain. | After Day 1 of treatment up to Week 48 | 
| Percentage of Participants With Sustained Virologic Response at Follow- upWeek 24 (SVR24) - Part B | SVR24 was defined as Hepatitis C virus (HCV) RNA level below lower limit of quantitation (LLOQ), target detected or not detected at Week 24 of post-treatment follow-up. HCV RNA level was measured using the Roche COBAS® TaqMan HCV Test v.2.0 (LLOQ) =25 IU/mL; limit of detection   10 IU/mL). | Follow-up Week 24 | 
| Percentage of Participants With Rash | All skin reactions involving rash or rash-like events that occurred on treatment were reported. | After Day 1 of treatment up to Week 48 |