HIV Patients With Chronic Hepatitis C Genotype 1 Infection Who Failed Previously to Peginterferon /Ribavirin

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and efficacy of a Response Guided Therapy of boceprevir 800 mg dosed three times a day (TID) orally (PO) in combination with Peginterferon (either alpha 2b or alpha 2a) and Ribavirin in HIV/HCV genotype 1 infected patients that failed to previous HCV therapy.

Official Title
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A Study to Evaluate Safety and Efficacy of Boceprevir-response Guided Therapy in Controlled HIV Patients With Chronic Hepatitis C Genotype 1 Infection Who Failed Previously to Peginterferon /Ribavirin Eudra CT2012-003984-23

Conditions
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Hepatitis C, HIV Infections, COINFECTION

Intervention / Treatment
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* Drug: boceprevir
* Drug: Ribavirin
* Drug: Peginterferon alfa-2a
* Drug: Peginterferon alfa-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study, subjects must have a qualifying regimen defined as peginterferon alfa-2a plus ribavirin or peginterferon alfa-2b plus ribavirin for a minimum of 12 weeks. If a subject has received more than one such regimen, the most recent regimen is considered the qualifying regimen. Subject must have previously documented chronic hepatitis C (CHC) genotype 1 infection. Subjects with other or mixed genotypes are not eligible. The HCV-RNA result at the screening visit must confirm genotype 1 infection and be ≥10,000 IU/mL. Subject must have a liver biopsy with histology consistent with CHC and no other etiology and/or Fibroscan assessment. In case of: No cirrhosis. Biopsies and/or Fibroscan must be within 18 months of screening visit. Cirrhosis. No specific length of time would be requested. All patients with cirrhosis must have an ultrasound 6 month within of screening visit. Patients must be on stable antiretroviral therapy including a CD4 cell count of more than 100 per mm3 and a HIV plasmatic viral load undetectable (it is < 50 copies/mL) for more than 6 months. Antiretroviral therapy must be Raltegravir-based (al least during the last 3 months). Subject must be ≥18 years of age. HIV treatment should not contain efavirenz (EFV), nevirapine (NVP), etravirine (ETV), didanosine (ddI), stavudine (d4T), zidovudine (AZT), or HIV protease inhibitors. Subject must weight between 40 kg and 125 kg. Subject and subject's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug. Subjects must be willing to give written informed consent and by investigator opinion be able to follow the protocol visit design. Exclusion Criteria: Subjects known to be coinfected with hepatitis B virus (HBsAg positive). Patients chronically infected with HCV genotype other than 1 CD4 cell count < 100 cel/mm3. Plasma HIV RNA more than 50 copies/mL Platelet count less than 80.000 /mm3 Subjects who required discontinuation of previous interferon or ribavirin regimen for a severe adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon. Treatment with ribavirin within 90 days and any interferon-alpha within 1 month of Screening. Treatment for hepatitis C with any investigational medication. Prior treatments with herbal remedies with known hepatotoxicity are exclusionary. Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study. History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis. Evidence of decompensate liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. Diabetic and/or hypertensive subjects with clinically significant ocular examination findings. Unstable or untreated pre-existing psychiatric condition. Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study. Any current evidence of substance abuse of alcohol or other drugs. Subjects receiving opioid agonist substitution therapy but not enrolled in an opiate substitution maintenance program.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: boceprevir + ribavirin + peginterferon<br>boceprevir 800 mg three times a day (v.o.) in combination with peginterferon (alfa-2b or alfa-2a) and ribavirin | Drug: boceprevir<br> <br> Drug: Ribavirin<br> <br> Drug: Peginterferon alfa-2a<br> <br> Drug: Peginterferon alfa-2b<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of sustained virological response (SVR) at week 24 | The primary efficacy endpoint is the achievement of SVR, defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If a subject is missing FW 24 data and has undetectable HCV-RNA level at FW 12, the subject would be considered an SVR. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of sustained virological response at weeks 2,4,8,12. | The proportion of subjects with virological response (eg. undetectable HCV-RNA at Weeks 2, 4, 8, or 12) in subjects who achieve SVR. | Weeks 2, 4, 8, 12 | 
| The proportion of subjects with undetectable HCV-RNA at FW 12. | The proportion of subjects with undetectable HCV-RNA at FW 12. | Week 12 | 
| The proportion of subjects with undetectable HCV-RNA at 72 weeks after randomization. | The proportion of subjects with undetectable HCV-RNA at 72 weeks after randomization. | Week 72 | 
| Number of adverse events | Safety: number of adverse events | From baseline to study completion (up to 72 weeks) | 
| Resistance of HCV after boceprevir (BOC) containing regimen | Resistance of HCV after boceprevir containing regimen. Blood samples will be collected at baseline and after HCV virological failure and resistance analysis will be done at the end of the study in a single Center (Hospital Clínic-Barcelona). | whenever resistance occurs during the study (from week 12 until the date the resistance occurs, assessed up to 72 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, HIV, Coinfection