A Phase 3, Safety and Efficacy Study of Boceprevir/Peginterferon Alfa-2a/ribavirin in Chronic HCV Genotype 1 IL28B CC Subjects
This is a randomized, open label, parallel-group, multi-center study of two boceprevir plus peginterferon alfa-2a/ribavirin (PEG2a/R) therapeutic regimens in treatment naïve subjects with chronic hepatitis C genotype 1 who have the IL28B CC. The regimens differ in the treatment for subjects who achieve HCV RNA undetectable at the end of the PEG2a/R 4 week lead-in. Subjects receive either PEG2a/R alone or BOC/ PEG2a/R.
Stratification: Baseline HCV RNA, high viral load ( and amp;gt;800,000 IU/mL) versus low viral load (≤ 800,000 IU/mL), and geographical region (US/Canada/Europe versus Asia/Other).
Subjects will be randomized by stratum in 1:1 ratio to the 2 treatment regimens: All subjects will receive a 4 week lead-in of PEG2a/R and be randomized to Arm 1 or Arm 2 at the end of the lead-in period (TW4).
Approximately 200 sites North America (US/Canada), EU, and Asia/other region, to enroll a total of 1250 subjects.
Approximately 50 subjects will be enrolled from this site (inclusive of screen failures).
The maximum time that a subject is expected to be enrolled in the study will depend upon their response to treatment. Screening, treatment, and treatment follow-up will require a maximum of 82 weeks.
A subject must meet all the criteria listed below to participate in the trial.
1. Each subject must be willing and able to provide written informed consent for the trial.
2. Subjects must be willing to give written informed consent for pharmacogenetic testing, and able to adhere to dose and visit schedules.
Note: Subjects who are unwilling to sign the informed consent for pharmacogenetic testing may be included into the trial, however, pharmacogenetic samples must not be obtained.
3. Each subject must be 18years of age.
4. Each subject’s weight must be ≥ 40 kg and ≤ 125 kg
5. Subject must have previously documented CHC genotype 1 infection where genotyping is performed as standard of care. If genotyping is not considered standard of care, then determination can be done at screening. Subjects with other or mixed genotypes are not eligible. The HCV-RNA result obtained from the central laboratory at the Screening Visit must confirm HCV genotype 1 infection with HCV RNA 10,000 IU/mL
6. Subjects must have IL28b CC allele gene (with SNP rs12979860)
7. Subject has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma. A liver biopsy done prior to screening is acceptable if:
Within 3 years of screening and the result was METAVIR (or equivalent) Stage 0 (F0) to 2 (F2).
Within 1 year of screening and the result was Stage 3 (F3).
If the prior liver biopsy was obtained outside the acceptable windows, a repeat biopsy may be performed, and the results must show no evidence of cirrhosis and hepatocellular carcinoma in order for the subject to be randomized in the study.
For countries where liver biopsy is not performed prior to treatment and where noninvasive tests (for e.g. FibroScan and/or FibroTest) are used for staging of liver disease, these results may be used to assess eligibility. Subjects with a documented FibroScan score of ≤9.5 kPa, or FibroTest score of ≤0.58 are allowed to be enrolled in the study. These non-invasive tests done prior to screening are acceptable if they were performed within 1 year of screening and meet the indicated cut-offs. If the prior non-invasive tests were not performed within 1 year of screening, results from one of these non-invasive tests is required before study drug dosing. If a subject has both liver biopsy and one of these non-invasive tests, whichever test demonstrates the presence of cirrhosis would be used to determine eligibility. In other words, if the liver biopsy shows cirrhosis, the subject is excluded, regardless of results of the non-invasive assay. If the liver biopsy does not show cirrhosis, but the non-invasive assay does, then the subject is still excluded.
8. Subject has had an ECG within 6 months prior to the screening visit (or between the screening visit and Day 1).
9. Subject and subject’s partner(s) must each agree to use acceptable methods of contraception as specified in Section 7.6.1 of the protocol for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study medication, or longer if dictated by local regulations. Postmenopausal women are not required to use contraception. Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period. Each sexually active male subject with a female partner(s) of child-bearing potential must also provide written informed consent to provide information regarding any pregnancy.
For the purposes of this protocol, a male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as: one who has undergone a successful vasectomy. A successful vasectomy is defined as: (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy.