Final Results of a roll-over study (107) with Telaprevir, Peginterferon Alfa-2A and Ribavirin in Prior Null Response, Partial Response, Viral Breakthrough or Relapse HCV Genotype 1 Patients After PR

Background and Aims: Study107 is an open-label rollover study of telaprevir (T) with peginterferon+ ribavirin (PR) in genotype-1 HCV patients who did not achieve sustained virologic response (SVR) following PR treatment in telaprevir Phase 2 studies.

Methods: Null responders (<1-log10 HCV RNA decrease at week-4 or <2-log10 at week-12), partial responders (≥ 2-log10 decrease at week-12, detectable at week-24), patients with viral breakthrough and relapsers from PROVE1/2/3 PR arms were eligible for treatment. Initially all patients received T 750mg q8h plus PR at standard doses for 12 weeks, followed by 12 weeks of PR (T12/PR24). Protocol was amended to allow partial responders, viral breakthroughs and relapsers with undetectable HCV RNA at weeks 4 and 12 (eRVR) to receive T12/PR24. Partial responders, viral breakthroughs and relapsers with detectable HCV RNA at week-4 and/or week-12 and null responders received an additional 24 weeks of PR (T12/PR48).

Results: Of 117 patients included in an ITT analysis, 97(83%) had baseline HCV RNA ≥ 800,000IU/mL, (69) 59% had genotype subtype 1a, 44(38%) had cirrhosis or bridging fibrosis, and 9(8%) were black. Viral breakthrough and relapse rates occurred in 25%, 23% of prior null responders; 10%, 22% of prior partial responders; 13%, 0% of prior viral breakthroughs; and 0%, 4% of prior relapsers.

The most frequent AEs (≥ 20%) were fatigue, flu-like-syndrome, nausea, diarrhea, pruritus, rash, headache, insomnia and anemia. Grade 3 rash and Grade 3 anemia were observed in 6(5%) and 6(5%) patients, respectively. Ten (9%) patients discontinued due to AEs, 5(4%) due to rash and 2(2%) to anemia.

Conclusions: Patients with prior relapse, breakthrough and partial response exhibited high SVR rates after 24 weeks of telaprevir-based regimen. High SVR rates were also observed in patients with previous null response after 48 weeks of therapy.

Table 1: Patients achieving SVR

a One prior partial responder and one prior relapser who discontinued all treatment prior to reaching week 12 of dosing were designated „unassigned“ to treatment group.
	T12/PR24 N=80	T12/PR48 N=35	Unassigned N=2a
Overall: n,%	47 (59)	18 (52)	2 (100)
Prior Null Responders: n/N,%	3/23 (13)	16/28 (57)	-
Prior Partial Responders: n/N,%	15/25 (60)	0/3 (0)	1/1 (100)
Prior Relapsers: n/N,%	23/25 (92)	2/3 (67)	1/1 (100)
Prior Viral Breakthrough: n/N,%	6/7 (86)	0/1 (0)	-

Hepatitis C - Roll-over study - Telaprevir - prior null-responder - prior partial responder