Rapid Hepatitis C Elimination Trial- A Pilot Study of Daclatasvir/Asunaprevir/BMS-791325 With or Without Ribavirin To Treat Hepatitis C Virus

Study Overview
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Brief Summary
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The purpose of this study is to determine whether treatment with Daclatasvir/Asunaprevir/BMS-791325, with or without ribavirin, for 8, 6, or 4 weeks is feasible for the treatment of genotype 1a chronic hepatitis C in patients without cirrhosis.

Official Title
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RHACE 1: Rapid HepAtitis C Elimination Trial - A Pilot Evaluation of Twice Daily Fixed Dose Combination Asunaprevir +Daclatasvir + BMS-791325 ± Weight Based Ribavirin in Treatment-Naïve, Non-cirrhotic Patients With Chronic Genotype 1a Hepatitis-C for Eight, Six or Four Weeks

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: DCV/ASV/BMS-791325
* Drug: DCV/ASV/BMS-791325 + RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects chronically infected with HCV genotype 1a HCV RNA ≥ 10,000 IU/mL at screening Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV), or HCV direct acting antiviral (DAA; protease, polymerase inhibitor, etc.) Exclusion Criteria: Evidence of cirrhosis Liver or any other organ transplant Current or known history of cancer within 5 years prior to enrollment Documented or suspected hepatocellular carcinoma (HCC) Not eligible for sofosbuvir + pegylated interferon + ribavirin therapy

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day for 8 weeks | Drug: DCV/ASV/BMS-791325<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) orally twice a day<br>* Other names: Fixed Dose Combination (FDC) of Daclatasvir/Asunaprevir/BMS-791325;|
| Experimental: Arm 2<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day for 6, 8 or 12 weeks | Drug: DCV/ASV/BMS-791325<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) orally twice a day<br>* Other names: Fixed Dose Combination (FDC) of Daclatasvir/Asunaprevir/BMS-791325;|
| Experimental: Arm 3<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day for 4 weeks | Drug: DCV/ASV/BMS-791325<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) orally twice a day<br>* Other names: Fixed Dose Combination (FDC) of Daclatasvir/Asunaprevir/BMS-791325;|
| Experimental: Arm A<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day for 8 weeks | Drug: DCV/ASV/BMS-791325 + RBV<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day<br>|
| Experimental: Arm B<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day for 6, 8 or 12 weeks | Drug: DCV/ASV/BMS-791325 + RBV<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day<br>|
| Experimental: Arm C<br>Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day for 4 weeks | Drug: DCV/ASV/BMS-791325 + RBV<br>* Fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg and BMS-791325 75 mg) tablet orally twice a day plus weight based ribavirin orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virologic Response | Proportion of treated subjects in each enrolled arm with sustained virologic response (SVR)12. SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) target detected or target not detected (TD/TND) at post treatment Week 12 | Post treatment week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | On treatment safety, as measured by frequency of serious adverse events (SAEs) and adverse events (AEs), discontinuations due to AEs, and rates and grades of select laboratory abnormalities including liver function tests and hematology laboratory abnormalities in each arm | Up to end of treatment (+7 days) | 
| Sustained virologic response | Proportion of treated subjects in each arm with SVR2, SVR4 and SVR 24, defined as HCV RNA < lower limit of quantification (LLOQ) target detected or target not detected (TD/TND) at post treatment Weeks, 2, 4, and 24 respectively | 2, 4 and 24 weeks post-treatment | 
| Post treatment virologic response | To assess the proportion of subjects who achieve sustained virologic response (SVR) 2, SVR4 and SVR24. | post treatment Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24) | 
| On treatment virologic response | To assess antiviral activity, as measured by the proportion of subjects who achieve HCV RNA <lower limit of detection (LLOD) and/or < lower limit of quantification (LLOQ) at each on treatment visit. | On-treatment Day 2 and Weeks 1, 2, 4, 6, 8 and 12 | 
| Virologic failure | To assess the proportion of subjects with virologic failure (including on treatment virologic breakthrough and relapse) and evaluate the emergence of viral resistant mutations. | On-treatment Day 2 and Weeks 1, 2, 4, 6, 8 and 12 and Post Treatment Weeks 2, 4, 12 and 24 | 
| Day 2 positive predictive value | To assess the predictive value of Day 2 virologic response on sustained virologic response (SVR) 12 | Post treatment Week 12 | 
| Interferon lambda genotype and virologic response | To compare the virologic response of subjects by genotype for interferon (IFN) lambda variants [' IL28B' and IFNL4-ΔG] | On-treatment Day 2 and Weeks 1, 2, 4, 6, 8 and 12 and Post Treatment Weeks 2, 4, 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, RNA Virus Infections, Antiviral Agents, Drug Resistance, Viral