Long-Term Follow-Up of Subjects in a Phase 1, 2, or 3 Clinical Trial in Which Boceprevir or Narlaprevir was Administered for the Treatment of Chronic Hepatitis C.

New antiviral therapies that directly inhibit replication of the hepatitis C
virus (HCV) are currently being developed. SCH 900518 and SCH 503034, hereafter
known as narlaprevir and boceprevir, respectively, are novel members of the
class of HCV non-structural protein 3 (NS3) protease inhibitors and are,
therefore, members of a class of direct antivirals for the treatment of HCV.
Treatment with either of these protease inhibitors in combination with
peginterferon and ribavirin (RBV) may represent a new therapeutic option for
patients with chronic hepatitis C
(CHC). The available information regarding the safety and efficacy of these
regimens is derived primarily from ongoing studies. Therefore, little is known
about the durability of the virologic response and long-term safety of this
therapeutic regimen. In this protocol, subjects will be followed for 36 months
after the end of their participation in a treatment protocol in order to
evaluate the durability of the antiviral response (for sustained responders)
and to characterize the long-term safety after use of one of these novel
therapeutic regimens.
During the treatment protocols, subjects were evaluated for the development of
HCV variants resistant to these novel agents. A number of resistant variants
have been identified both in vitro and in vivo. However, the clinical
significance of a greater proportion of such variants, and the effect of
stopping therapy upon the specific pattern of HCV mutational variation, either
known or suspected to confer resistance to narlaprevir or boceprevir, is not
well established. In the present study, for subjects with detectable HCV RNA,
sequence analyses will be performed at
regular intervals in order to characterize the natural history of these
variants following treatment with these new antivirals. In general, these
variants are usually less fit and, therefore, may be replaced by wild-type
virus once the selection pressure of the direct inhibitor is removed.

This study will be conducted in two parts as described below:
Part 1 will include subjects who participated in a Phase 1, 2, or 3 clinical
study in which boceprevir was administered.
Part 2 will include subjects who participated in a Phase 1, 2, or 3 clinical
study in which narlaprevir was administered.
Parts 1 and 2 have three primary objectives:
* Confirm the durability of the virologic response in subjects with chronic
hepatitis C who were sustained responders 24 weeks post-treatment in the
previous study.
* Characterize the long-term safety in subjects who received at least one dose
of study medication in a previous Phase 1, 2, or 3 boceprevir or narlaprevir
clinical study.
* Characterize the natural history of HCV sequence variants in subjects who
received at least one dose of study medication in a previous Phase 1, 2, or 3
boceprevir or narlaprevir clinical study

This is a long-term follow-up multicenter study in subjects in a Phase 1, 2, or
3 Clinical Trial in Which Boceprevir or Narlaprevir was Administered for the
Treatment of Chronic Hepatitis C and have received at least one dose of any
studymedication (peginterferon, ribavarin, boceprevir or narlaprevir). The
study will be conducted in up to 215 sites worldwide. No drug therapy will be
administered as part of this study.
There will be 8 scheduled study visits, the first 3 separated by 3-month
intervals, and the last 5 separated by 6-month intervals.

No medication will be given under this protocol and the risks are minimal (only
foreseeable risk is rare complication due to venous blood draw).

Burden patients: 8 vists 30-45 minutes per visit and 8 x blood draw

Since no treatment will be administered in this study, the benefits to the
subject will be:
1. Long-term follow-up care to monitor if safety issues arise over the next 3
years,
2. Long-term follow-up care to monitor if any sustained responders from the
previous study relapse over the next 3 years,
3. Long-term follow-up to characterize the natural history of HCV sequence
variants in subjects who developed sequence variants while participating in a
treatment protocol that included Boceprevir or Narlaprevir.

Indirectly, the subject's participation in this study may contribute to the
further understanding of the treatment of chronic hepatitis C.