Efficacy and Safety Evaluation of a Regimen Consisting of Peginterferon Lambda-1a + Ribavirin + Daclatasvir (Lambda + RBV + DCV) in HCV Genotype 1b Treatment naïve Patients or Prior Relapsers to Peginterferon Alfa + Ribavirin (Alfa + RBV) Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin

Official Title
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A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients chronically infected with HCV Genotype-1b Naïve to prior treatment or documented evidence of relapse after completion of the prescribed duration of treatment (duration may be 24 or 48 weeks, to be determined based upon local guidelines) HCV RNA viral load ≥100,000 IU/mL at screening Patients with compensated cirrhosis are permitted Exclusion Criteria: Infection with Hepatitis C virus (HCV) other than Genotype-1b Positive Hepatitis B surface antigen (HBsAg) or Human immunodeficiency virus (HIV)-1/HIV-2 antibody test at screening Evidence of chronic liver disease caused by diseases other than chronic HCV infection Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening Current evidence or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria Laboratory values: Hemoglobin <12.0 g/dL (males) or <11.0 g/dL (females) Platelets <90,000/mm3 Total serum bilirubin ≥2 mg/dL (unless due to Gilbert's disease)

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peginterferon Lambda-1a + Ribavirin + Daclatasvir<br>Peginterferon Lambda-1a 180 µg solution for subcutaneous injection, once a week for 24 Weeks Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 weeks Daclatasvir 60 mg tablets by mouth, once a day for 12 weeks | Biological: Peginterferon Lambda-1a<br> <br> * Other names: BMS-914143;Drug: Ribavirin<br> <br> * Other names: Copegus®;Drug: Daclatasvir<br> <br> * Other names: BMS-790052;|
| Experimental: Peginterferon Alfa-2a + Ribavirin + Telaprevir<br>Peginterferon Alfa-2a 180 µg solution for subcutaneous injection, once a week for 24 to 48 weeks depending on response Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 to 48 weeks depending on response Telaprevir 375 mg tablets [2250 mg total daily dose: subjects should take 750 mg (two 375 mg tablets) orally three times a day, approximately 7-9 hours apart) for 12 weeks | Biological: Peginterferon Alfa-2a<br> <br> * Other names: Pegasys®;Drug: Ribavirin<br> <br> * Other names: Copegus®;Drug: Telaprevir<br> <br> * Other names: Incivek®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12) |  | Post treatment follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve SVR12 in treatment-naive subjects |  | Post treatment follow-up Week 12 | 
| Proportion of subjects with rash related dermatologic events |  | Up to 12 weeks of treatment | 
| Proportion of subjects who develop treatment emergent cytopenic abnormalities | Treatment emergent cytopenic abnormalities [anemia as defined by Hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750/mm3, and or thrombocytopenia as defined by platelets < 50,000/mm3] | Up to 48 Weeks | 
| Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms |  | Up to 48 Weeks | 
| Proportion of subjects who achieve SVR24 [Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Lower limit of quantitation (LLOQ)] at post-treatment follow-up Week 24 | SVR24 = Sustained virologic response at post treatment follow-up Week 24 | Post treatment follow-up Week 24 | 
| Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up |  | Maximum of 72 weeks | 
| Proportion of subjects who achieve SVR12 with a 24-week treatment regimen |  | Post treatment follow-up Week 12 | 
| Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment) |  | Weeks 4 and 12 of treatment | 
| Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up |  | Maximum of 72 weeks | 
| Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT) |  | Maximum of 72 weeks | 
| Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT | Psychiatric symptoms (depression, irritability or insomnia) | Maximum of 48 weeks | 
| Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses | For each SNP in each candidate gene, allele and genotype frequencies will be summarized by treatment regimen | Post-treatment follow-up Week 12 | 
| Resistant variants associated with virologic failure through end of follow-up |  | Maximum of 72 weeks |