BIPI 1220.19: Safety and Efficacy of 120 mg and 240 mg BI 201335 once daily in combination with pegylated interferon alpha 2a and ribavirin for treatment of chronic Hepatitis C (HCV) genotype 1 infection in HIV/HCV-co-infected patients. A multinational, randomized, parallel group, open-label trial.
This is a multi-national, randomised, parallel group, open-label trial. It is planned to include approximately 316 HCV genotype 1/HIV-1 coinfected patients who either have not received prior treatment for HCV with any interferon alpha, ribavirin, or other direct antiviral agent (DAA) or who relapsed after completion of treatment with a peginterferon containing regimen for HCV (approximately 60 patients).
All patients eligible to be randomised or directly assigned* at study entry will receive one of the following treatment patterns:
A. 240 mg BI 201335 QD for 12 or 24 weeks^ combined with PegIFN/RBV for 24 or 48 weeks+
B. 120 mg BI 201335 QD for 24 weeks combined with Peg IFN/RBV for 24 or 48 weeks+
*Directly assigned to:
1. Group A 240 mg: Patients taking efazirenz or patients enrolled prior to amendment 1
2. Group B 120 mg: Patients taking darunavir/ritonavir, or atazanavir/ritonavir
^ Patients receiving 240 mg who have not discontinued BI 201335 will be randomized at Week 12 to stop or continue BI 201335 until Week 24
+ Patients in both groups who have achieved Early Treatment Success (ETS: defined as HCV RNA and amp;lt; 25 IU/mL, detected or undetected at Week 4 and HCV RNA and amp;lt; 25 IU/mL, undetected at Week 8) and have not discontinued any study drug will be randomized at Week 24 to stop or continue PegIFN/RBV until Week 48. All other patients will not be randomized and will receive PegIFN/RBV until Week 48.
All randomizations will be stratified by HCV 1 sub-genotype.
1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detectable
HCV RNA at screening in addition to:
* Positive anti-HCV antibodies or detectable HCV RNA at least 6 months prior to screening
2. HCV genotype 1 infection confirmed by genotypic testing at screening
3. HCV RNA >= 1,000 IU/ml at screening.
4. HCV Naive or HCV relapser defined as the following:
* Treatment-naive to interferon, pegylated interferon and ribavirin, or
* Prior relapser: Undetectable HCV RNA (based on an assay considered sensitive at the time of treatment) at the end of treatment with a pegylated interferon-based regimen, but HCV RNA detectable within 24 weeks of treatment follow up
5. Documentation of liver biopsy within 3 years or fibroscan within 6 months prior to
* Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies obtained more than 3 years before randomisation enrolment need not be repeated. Biopsies may be waived for patients who would be placed at risk from the procedure. Inability to do a liver biopsy in patients at risk for the procedure should not exclude such patients from a trial.
* Subject[Single Quote]s documentation of the last liver biopsy or fibroscan performed will be requested at the randomization visit.
6. Age 18 to 70 years.
7. Chronic HIV-1 infection confirmed by HIV-1 viral load testing at screening and documented for a period of at least 6 months prior to screening by HIV-1 viral load, or HIV-1 Western blot.
8. ARV-treatment naive or patients on stable HAART, defined as the following
* ARV-Naive: Never received combination antiretroviral therapy, or never received monotherapy with any of the allowed antiretrovirals Raltegravir, or Elvitegravir, or an experimental antiretroviral.
Peripheral CD4 T cell count >=500 cells/mm3 at screening visit, and HIV plasma RNA <100,000 copies/mL.
Note: According to judgment by the investigator ARVxnaive patients should only be enrolled if it is expected that they will not require initiation of HAART during the 8 weeks following initiation of treatment with BI 201335 and PegIFN/RBV. In the event that the patient needs to start HAART during the trial, please see Appendix 10.7 for further guidance.
* Patients on stable HAART: HIV-1 plasma RNA <40 copies/mL at screening and <50 copies/mL for at least 6 months prior to initial randomisation, and including a maximum of 2 HIV VL blips during this period. Must be on an acceptable combination of antiretrovirals which are allowed in the study for at least 6 weeks prior to randomisation; peripheral CD4 T cell count >= 200 cells/mm3 at screening visit.
* Patients on an acceptable ATZ/RTV-containing HAART regimen must have total bilirubin < or equal to 2.5 ULN at screening, and must participate in the intensive ATZ/RTV PK sampling.
* Patients on stable HAART: Must be on stable Raltegravir/Truvada therapy for at least 8 weeks prior to randomization. Peripheral CD4 T cell count >=200 cells/mm3 at screening visit, and HIV plasma RNA <48 copies/mL for at least 6 months prior to randomization.
9. Female patients:
a. with documented hysterectomy,
b. who have had both ovaries removed,
c. with documented tubal ligation,
d. who are post-menopausal with last menstrual period at least 12 months prior to screening, or
e. of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the
date of screening until 7 months after the last dose of ribavirin.
f. Medically accepted methods of contraception for females in this trial are ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intra-uterine device.
a. who are documented to be sterile, or
b. who are without pregnant female partner and consistently and correctly use a condom while their female partner (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor).
10. No AIDS-defining illness during 6 months prior to screening
11. Karnofsky score >70
12. Signed informed consent form prior to trial participation