An Open-Label Phase 3 Study of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys(RegisteredTM)), and Ribavirin (Copegus(RegisteredTM)) in Subjects Coinfected With Genotype 1 Hepatitis C Virus and Human Immunodeficiency Virus Type 1 (HCV/HIV-1)
This is an open-label, single-arm, multicenter study. The Screening Period will be approximately 4 weeks, the Treatment Period up to 48 weeks, and the Follow-up Period at least 48 weeks with maximal follow-up of 96 weeks, depending on viral responses. all subjects will receive telaprevir in combination with Peg iFn and RBV for the first
Population a subjects (treatment naive or previous treatment-relapser) who achieve eRVR will complete an additional 12 weeks of Peg-iFn/RBV after the initial 12 weeks of telaprevir, Peg-iFn and RBV, whereas those who do not achieve eRVR will complete an additional 36 weeks of Peg-iFn/RBV treatment.
Population B subjects (previous null or previous partial responder) will complete 48 weeks of Peg-iFn/RBV treatment, including the 12 weeks of telaprevir.
1. Subjects must have chronic, genotype 1a or 1b, hepatitis C with HCV RNA >1000 IU/mL by Roche Taqman(RegisteredTM) v2 at Screening. Genotype and subtype must be confirmed at Screening by Versant(RegisteredTM) LiPA HCV v2.0. Diagnosis of HCV must have been documented by HCV serology test or HCV RNA >6 months before Screening
2. Population A subjects must be 1 of the following:
a. HCV Peg-IFN/RBV treatment naive (received no prior HCV therapy)
b. Peg-IFN/RBV prior treatment with relapse (documented undetectable HCV RNA level at the planned EOT of at least 42 weeks duration [HCV RNA evaluated within 6 weeks after the last dose of medication] but did not achieve SVR24. Start and stop dates of treatment must be documented. The last dose of Peg-IFN/RBV must have been at least 12 weeks before Screening)
3. Population B subjects must not have achieved SVR24 after at least 1 prior course of Peg-IFN/RBV therapy of standard duration. The last dose of Peg-IFN/RBV must have been at least 12 weeks before Screening. Population B subject must be 1 of the following:
a. Failure to decrease HCV RNA by at least 2 logs after 12 weeks of therapy (prior null-responder)
b. A >=2 log decrease in HCV RNA at 12 weeks of prior Peg-IFN/RBV treatment, but never achieved undetectable HCV RNA while on treatment (prior partial responder)
4. Subject must have a diagnosis of HIV-1 infection >6 months before Screening documented by 1 of the following:
a. ELISA with confirmatory Western blot
b. Other confirmed anti-HIV-1 antibody test, HIV-1 antigen, or Plasma HIV-1 RNA
5. In the 6 months before Screening, subject must have at least one CD4 count >200 cells/mm3 and no value <200 cells/mm3
6. In the 6 months before Screening, subject must have at least one HIV-1 RNA below the limit of detection with either no values >200 copies/mL by ultrasensitive assays or not greater than the lower limit of detection for assays with a limit of 400 copies/mL.
7. At Screening, positive HIV antibody (ELISA with or without confirmatory Western blot)
8. At Screening, CD4 count >200 cells/mm3
9. At Screening, HIV-1 RNA <50 copies/mL by Roche Taqman HIV-1 RNA v2
10. Taking 1 of the following permissible HAART regimens for HIV continuously >=12 weeks before Day 1 without switches during that time: efavirenz, ATV/r or raltegravir-based regimens that contain nucleos(t)ide backbones of tenofovir or abacavir plus lamivudine or emtricitabine
11. Male and female subjects 18 to 65 years of age, inclusive
12. Laboratory values within the following acceptable ranges at Screening
a. Absolute neutrophil count (ANC) >1500 cells/cmm. If Black race then a result >1200 cells/cmm is acceptable.
b. Alanine aminotransferase (ALT) <5 x upper limit of normal (ULN)
c. Aspartate aminotransferase (AST) <5 x ULN
d. Potassium within normal limits
e. Creatinine clearance >70 mL/min
f. Hepatitis B virus DNA and surface antigen, negative in serum
g. Hemoglobin >11 g/dL for women, >12 g/dL for men
h. Platelet count >90000 x106/L
i. Thyroid stimulating hormone (TSH) (with reflex to Free T4) within normal range, adequately controlled with thyroid treatment or abnormal but not clinically significant as judged by the investigator.
j. Uric acid within normal limits
13. Baseline evidence of the absence or presence of cirrhosis at Screening by FibroSure
(FibroTest component cutoff greater than 0.74 for cirrhosis), FibroScan (cirrhosis cutoff by standard criteria or manufacturer[Single Quote]s instruction as applicable in countries where approved), or documented liver biopsy result within 1 year of Day 1. If a previous liver biopsy result showed evidence of cirrhosis at any time in the past then no current testing is required to show evidence of cirrhosis.
14. Female subjects must not be pregnant (negative pregnancy test at Screening and Day 1) or planning to become pregnant within 6 months after the last dose of ribavirin, or they must be permanently sterile or otherwise of nonchildbearing potential. Female subjects must also not be breastfeeding. If of childbearing potential, agree to use 2 effective methods of contraception from Screening through 6 months after the last dose of RBV.
15. Male subjects who have a female partner of childbearing potential agree to use 2 effective
methods of contraception from Screening through 7 months after the last dose of RBV.
16. Willing and able to refrain from the concomitant use of any restricted medications, substances or foods as indicated in Section 10.3 from 14 days before Day 1 through Week 12.
17. Able to read and understand and willing to sign the informed consent form (ICF) and abide by study restrictions.