Clinical trial NCT01443923
Conditions: Hepatitis HIV/AIDS
Keywords: Hepatitis Immunological Response Virological Response Resistance Mutations Viral Kinetics Hepatitis C HCV
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2011-09-01; Completion date: 2013-09-01
Enrollment: 4 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- Standard treatment for the hepatitis C virus (HCV) is a combination of the drugs peg-IFN and ribavirin. However, this treatment is not very effective in people with a serious type of HCV (HCV genotype 1) and also in people who have human immunodeficiency virus (HIV) coinfection. Researchers want to add a new drug, boceprevir to see if it can improve treatment results in people with both HCV genotype 1 and HIV. Boceprevir used in combination with peg-IFN and ribavirin has been recently approved for the treatment of people with HCV genotype 1 infection only, and is currently being studied in those with HIV and HCV.

Objectives:

\- To test boceprevir, peg-IFN, and ribavirin as a treatment for HCV genotype 1 in people with HCV monoinfection compared to those with both HIV and HCV infections.

Eligibility:

* Individuals at least 18 years of age who have HCV genotype 1 infection, and have not received interferon treatment for HCV
* Half of the study participants will also have HIV infection.

Design:

* Participants will be screened with a medical history and physical exam. They will also have blood and urine tests.
* Participants will also have heart and liver function tests, and answer questions about mood and depression.
* Those in the study will receive ribavirin tablets to take twice a day, and peg-IFN to inject under the skin weekly.
* Two weeks after starting treatment, participants will have blood tests to study the treatment.
* Four weeks after starting treatment, participants will start taking boceprevir three times a day.
* Participants will have regular study visits with blood samples and other tests. The length of therapy will depend on the level of virus detected in the blood at several clinic visits. Those who do not respond well to the medicines at 12 weeks will stop treatment. The full length of treatment is 48 weeks.

Detailed description:
Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States, an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. A combination of ribavirin (RBV) and pegylated interferon (peg-IFN) is the currently recommended therapy for chronic HCV infection. However, this therapy achieves viral clearance in only 19% to 52% of patients infected with HCV genotype 1 and 76% to 80% of patients infected with genotypes 2 and 3. Current therapy is also associated with a high incidence of adverse events and low cure rates in several populations. Novel therapies that do not rely on an interferon backbone will be required to enhance cure rates in various populations. Recent data show that adding an HCV serine protease inhibitor (such as boceprevir \[BOC\]) to peg-IFN and RBV results in HCV eradication rates of 70% to 80% among HCV-monoinfected subjects. However, whether human immunodeficiency virus (HIV)-infected subjects will have similar rates of response to triple combination therapy is presently not known. Previous data have suggested that HIV-infected patients with chronic HCV infection have much lower eradication rates to peg-IFN and RBV than HCV-monoinfected subjects. This study will explore whether HIV/HCV-coinfected subjects have a lower response rate to a BOC/peg-IFN/RBV regimen than HCV-monoinfected subjects. Participants who have chronic hepatitis C genotype 1 monoinfection (N=50) or coinfection with HIV-1 (N=50), and who are na(SqrRoot) ve to IFN-based HCV treatment, will receive combination therapy with BOC (800 mg three times a day, every 7 to 9 hours, with food), weekly peg-IFN alpha-2b (1.5 mcg/kg/week) and twice daily RBV (weight based) for a maximum of 44 weeks, after a 4-week lead-in of peg-IFN and RBV. BOC received recent FDA approval for treating HCV monoinfection in combination with peg-IFN and RBV, and the approved labeling will be followed in this study. The primary endpoint is comparative efficacy in HCV-monoinfected and HIV/HCV-coinfected subjects. Secondary endpoints include determination of host predictors for therapeutic response, emergence of resistance biomarkers, and early viral kinetics. The findings from this study will aid in the understanding of whether HIV infection affects HCV antiviral and host responses to combination therapy using BOC/peg-IFN alfa-2b/RBV.

Arms: arm 1: Hepatitis C Mono-infected arm 2: Hepatitis C and HIV co-Infected
Interventions: intervention 1: Boceprevir intervention 2: Peg-Interferon-alfa 2B intervention 3: Ribavirin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: