Efficacy of GZR/EBR in Early Chronic Hepatitis C in HIV/HCV Co-infected Patients

Study Overview
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Brief Summary
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Evaluate the efficacy of 12 or 8 weeks treatment with Grazoprevir/Elbasvir in Early Chronic Hepatitis C GT1,4 in HIV co-infected patients and evaluate the safety and tolerability of Grazoprevir + Elbasvir in HIV-HCV co-infected patients.

Detailed Description
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Genotype 1b: 8 weeks treatment with Grazoprevir/Elbasvir Genotype 1a and 4: 12 weeks treatment with Grazoprevir/Elbasvir

Official Title
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Efficacy of GZR/EBR in Early Chronic Hepatitis C in HIV/HCV Co-infected Patients

Conditions
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HIV, Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir 100 mg/d 8 weeks
* Drug: Elbasvir 50 mg/d 8 weeks
* Drug: Grazoprevir 100 mg/d 12 weeks
* Drug: Elbasvir 50 mg/d 12 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Patients with early chronic hepatitis C (Genotype 1 or 4) which is defined as chronic hepatitis C with known episode of AHC within the last 4 years including those who failed to PEG/RBV or those who never received therapy for AHC. AHC infection is diagnosed on the basis of documented HCV-RNA positivity (> 10.000 IU/mL) and anti-HCV seroconversion. No history of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result <8 kPa Be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load. Be on stable HIV Antiretroviral Therapy (ART) for at least 8 weeks prior to study entry using a dual NRTI backbone of tenofovir or abacavir Exclusion Criteria: < 18 years of age Patients with chronic hepatitis C genotypes other than 1 or 4. History of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs/symptoms of advanced liver disease Have liver disease staging assessment as follows: Fibroscan performed within 3 previous months of Day 1 of this study showing result > 8kPa Not be HIV-1 infected, documented by any licensed rapid HIV test and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load. Due to known or suspected drug-drug interactions, for the purpose of this study, the use of Non Nucleoside Reverse Transcriptase Inhibitors, Inhibitors or Protease Inhibitors against HIV will be not allow.

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: Genotype 1b<br>Grazoprevir 100 mg/d during 8 weeks. Elbasvir 50 mg/d during 8 weeks. | Drug: Grazoprevir 100 mg/d 8 weeks<br>* Patients with 1b HCV genotype will be received treatment with Grazoprevir (100 mg) during 8 weeks.<br>* Other names: MK-5172 100 mg;Drug: Elbasvir 50 mg/d 8 weeks<br>* Patients with 1b HCV genotype will be received treatment with Elbasvir (50mg) during 8 weeks.<br>* Other names: MK-8742 50 mg;|
| Experimental: Genotype 1a and 4<br>Grazoprevir 100 mg/d during 12 weeks. Elbasvir 50 mg/d during 12 weeks. | Drug: Grazoprevir 100 mg/d 12 weeks<br>* Patients with 1a or 4 HCV genotype will be received treatment with Grazoprevir (100 mg) during 12 weeks.<br>* Other names: MK-5172 100 mg;Drug: Elbasvir 50 mg/d 12 weeks<br>* Patients with 1a or 4 HCV genotype will be received treatment with Elbasvir (50mg) during 12 weeks.<br>* Other names: MK-8742 50 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response. | Sustained virological response 12 (SVR12) defined as HCV-RNA undetectable at post-treatment. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reinfection rate | Evaluate the reinfection rate during 1 year of follow-up Sustained virological response defined as HCV-RNA undetectable at post-treatment. | 1 year | 
| Evaluate the safety and tolerability by means of number of participants with treatment-related adverse events. | number of adverse events treatment-related assess in 62 patients. | 2 years | 
| Evaluate the emergence of of viral resistance-associated variants (RAV) resistant to MK-5172 and MK-8742. during the follow up. | In case of viral failure confirmation during the follow up, viral resistence-associated variants will be assess by samples genotyping HCV protease and NS5A gene at baseline and after the viral failure. | 2 years |