Telaprevir Open-Label Study in Co-Infected Patients
Telaprevir Open-Label Study in Co-Infected Patients
The purpose of this study is to collect safety and tolerability data on telaprevir treatment
 in combination with Peg-IFN-alfa and RBV in patients with HIV/genotype 1 chronic HCV
 coinfection with severe fibrosis or compensated cirrhosis who are not eligible for enrollment
 into an ongoing clinical study of telaprevir.
In this study, all patients will receive open-label (all people involved know the identity of
 the intervention) telaprevir in addition to Peg IFN-alfa and RBV for treatment of hepatitis C
 virus (HCV) and protocol permissible treatments for HIV. Chronic hepatitis C infection causes
 inflammation of the liver which can potentially cause long-term complications of the current
 liver disease (fibrosis or cirrhosis). Therefore it is important the patient is treated for
 this infection. Telaprevir is an experimental medication that has been tested for the
 treatment of hepatitis C infections in several previous studies in more than 2500 patients.
 Telaprevir is a member of a new class of drugs being developed for chronic hepatitis C:
 Direct Acting Antiviral (DAA) agents. Unlike pegylated interferon (Peg-IFN) and ribavirin
 (RBV), DAA agents act directly on the hepatitis C virus (HCV) replication cycle. The aim of
 the telaprevir treatment is to eradicate the Hepatitis C virus out of the patient's body.
 This can be measured by testing the amount of a certain part of this Hepatitis C virus,
 called the Ribonucleic acid (RNA [HCV RNA]) in their blood. It is possible that the patient
 will not respond to the therapy and the levels of HCV RNA in their blood will not decrease or
 even increase. Based on these results it might be decided the patient will not benefit from
 treatment and he/she need to stop the telaprevir only or all medication for their hepatitis C
 infection. The doctor will keep them informed about the patient's reaction to the treatment
 and will take the necessary measurements as prescribed by the study protocol and routine
 medical practice. During the study the patient will simultaneously be treated with the
 therapy that the doctor would normally prescribe for treatment of their chronic hepatitis C
 infection: "ribavirin (RBV)" and "pegylated interferon alfa (PEG-INF-alfa)". Telaprevir is
 always administered in combination with RBV and PEG-IFN-alfa. In function of the patient's
 specific HIV status, the doctor has prescribed, or not, a specific treatment that the patient
 will continue to take during the study. This treatment could be: (a) efavirenz, tenofovir
 disoproxil fumarate (TDF), plus either emtricitabine or lamivudine, (b) efavirenz, abacavir,
 plus either emtricitabine or lamivudine, (c) ritonavir-boosted atazanavir, TDF, plus either
 emtricitabine or lamivudine, (d) ritonavir-boosted atazanavir, abacavir, plus either
 emtricitabine or lamivudine, (e) raltegravir, TDF, plus either emtricitabine or lamivudine,
 (f) raltegravir, abacavir, plus either emtricitabine or lamivudine or (g) etravirine, TDF,
 plus either emtricitabine or lamivudin, (h) etravirine, abacavir, plus either emtricitabine
 or lamivudine, (i) rilpivirine, TDF, plus either emtricitabine or lamivudine, (j)
 rilpivirine, abacavir, plus either emtricitabine or lamivudine, (k) no treatment. In an
 interim analysis of a Phase 2a study, human immunodeficiency virus (HIV)-1/HCV genotype 1
 coinfected patients currently receiving HIV therapy who had telaprevir added to Peg
 IFN-alfa-2a and RBV regimen for treatment of their HCV genotype 1 infection had a higher HCV
 RNA response (undetectable HCV RNA) at Weeks 4 and 12 than those who received only the
 Peg-IFN-alfa-2a and RBV regimen. These responses were sustained through Week 24, with 73.7%
 of patients who had telaprevir added to the Peg-IFN-alfa-2a and RBV regimen and 54.5% of
 patients who received only the Peg-IFN-alfa-2a and RBV regimen also achieving undetectable
 HCV RNA at Week 24. Patients with severe fibrosis or cirrhosis have a lower likelihood of
 sustained virologic response (SVR) and also have the greatest risk of liver failure,
 hepatocellular carcinoma (HCC), and death. Administering telaprevir in this difficult to
 treat population may reduce the risk of long-term complications associated with HCV in
 patients with HIV/HCV genotype 1 coinfection. All patients eligible to enter the study will
 receive telaprevir (750 or 1,125 mg every 8 hours based on their Highly Active Antiretroviral
 Therapy (HAART) regimen) during the first 12 weeks of the study in combination with Peg IFN
 alfa/RBV. Patients will subsequently be treated with Peg-IFN-alfa/RBV for an additional 36
 weeks. The total duration of Peg-IFN-alfa/RBV will be 48 weeks. HCV RNA levels should be
 measured at Weeks 4, 12, 24 and 48. All patients should have a posttreatment follow-up visit,
 including measurement of plasma HCV RNA levels, performed 24 weeks after the last
 administered dose of treatment. Note that in certain countries, an additional main objective
 of the study is to provide Early Access to telaprevir in this population.
Inclusion Criteria: - Have diagnosis of HIV-1 or HIV-2 infection, or HIV-1 and HIV-2
 coinfection for more than 6 months before the screening visit. - Should have been on a
 stable permissible HAART regimen for more than 8 weeks before Day 1 without switches. OR
 Not on a HAART regimen and not expected to start HIV treatment during the study, ie, have
 CD4 count of ≥500 cells/mm3 and a HIV-1 and/or HIV-2 viral load ≤50,000 copies/mL at
 screening - If on stable permissible HAART regimen, have CD4 count ≥200 cells/mm3 or ≥15%
 and HIV-1 and/or HIV-2 viral load <50 copies/mL for at least 6 months before starting
 treatment is recommended - Have evidence of HCV infection genotype 1 (molecular assay) -
 Have a quantifiable plasma HCV RNA Exclusion Criteria: - Is eligible for enrollment into an
 ongoing clinical study of telaprevir - Is infected or coinfected with HCV of another
 genotype than genotype 1 - Has a contraindication to the administration of Peg-IFN-alfa or
 RBV, or medical history or laboratory values that preclude treatment with Peg-IFN-alfa or
 RBV according to the respective local prescribing information - Have any contraindication
 to the currently prescribed HAART regimen at screening. Note: Patients who have a
 contraindication to a nonprescribed permissible HAART medication are not excluded. -
 Positive human leukocyte antigen (HLA)-B5701 genotyping result at screening (or documented
 result prior to screening) if abacavir is a component of HAART