Earlier, I had read the following passage from Adam's column and overlooked the meaning of 'SVR12 data' from this 'Arm D' if the trial has been run as stated by him: ......... "According to criteria built into the Prove 1 study design, Arm D patients have to achieve undetectable levels of virus at four weeks AND 10 weeks of treatment in order to stop treatment altogether at 12 weeks. If a patient doesn't meet this interim efficacy hurdle, doctors will order patients to continue receiving interferon and ribavirin for an extended period beyond 12 weeks." ........... I capped AND to emphasize. If the above is the true design, you cannot get any quantitative SVR12 from Arm D. The trial selects early responders who score UND at the end of both 4wk and 10wk of treatment, and determines whether they would be UND 12 weeks after 12 wk treatment. Those who did not achieve UND either at the 4 wk OR 10 wk point are not qualified to contribute to this trial because the trial design is different from the rest of participants and their number is most likely too small(am I too optimistic here?) to yield meaningful data. EASL report, if it has only Arm D data, has little significance beyond finding the correlation between early response and SVR12. Of course, if the correlation is close to 1 (like >95%), it will be great. Hopefully, EASL reports more PROVE 1 data other than Arm D's.
Looks like they will report all arms. And complete detail for those in the arms taking 0 or 12 weeks of post telaprevir IFN and RBV. They will be missing the 36 week post IFN and RBV and the control arm.
RESULTS OF AN INTERIM ANALYSIS OF A PHASE 2 STUDY OF TELAPREVIR (VX-950) WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN PREVIOUSLY UNTREATED SUBJECTS WITH HEPATITIS C
J.G. McHutchison 1, G.T. Everson 2, S. Gordon 3, I. Jacobson 4, R. Kauffman 5, L. McNair 6, A. Muir 7
1 Division of Gastroenterology, Duke University and Duke Clinical Research Institute, Durham, NC, USA; 2 Department of Hepatology, University of Colorado Health Sciences Center, Denver, CO, USA; 3 Henry Ford Health System, Detroit, MI, USA; 4 Division of Gastroenterology and Hepatology, Weill Medical College of Cornell, New York, NY, USA; 5 Vertex Pharmaceuticals, Cambridge, MA, USA; 6 Vertex Pharmaceuticals, Cambridge, MA, USA; 7 Division of Gastroenterology, Duke University and Duke Clinical Research Institute, Durham, NC, USA
Background: The VX05-950-104 study (PROVE1) is a randomized, placebo-controlled Phase 2 study of telaprevir (TVR), in combination with peginterferon alfa-2a (Peg-IFN-2a) and ribavirin (RBV), in naive subjects with genotype 1 hepatitis C infection. We report the results of a planned interim safety and data analysis. A total of 250 subjects received study drug. Methods: Subjects were randomized into 4 groups; 3 groups were randomized to receive TVR 750 mg q8h, Peg-IFN-2a 180 ug/week, and RBV 1000-1200 mg/day for 12 weeks followed by 0, 12 or 36 weeks of Peg-IFN-2a and RBV (TVR/PR groups). The control group was randomized to receive up to 48 weeks of Peg-IFN-2a/RBV, with TVR-matched placebo for the first 12 weeks. This planned interim analysis was performed when the first 80 enrolled subjects had completed 12 weeks of dosing. All subjects in the TVR groups received the same treatment through Week 12; these groups were pooled for this analysis. Results: The total incidence of adverse events was similar in the control and TVR/PR groups (75% vs. 80%). Discontinuations due to adverse events were more frequent in the TVR/PR group (9% vs. 3%). Rashes were more common and some were more severe, and gastrointestinal (GI) events were more common, in the TVR/PR group. In subjects for whom results were available at Week 12, the proportion of subjects with undetectable HCV RNA at Week 12 was 88% in the TVR/PR group, and 52% in the control group (p=0.0001). (Taqman assay: LOD 10 IU/mL). Conclusions: TVR/PR produced a higher frequency of HCV RNA undetectability than Peg-IFN-2a/RBV alone, in this 12-week interim analysis. The adverse event profile was similar in type of events, but rash and GI events were more common in the TVR/PR group. The Independent Data Monitoring Committee reviewed the data and recommended no changes to the study. An interim analysis, including data up to 12 weeks on-study in all subjects, as well as SVR12 data in subjects who have stopped all treatment at 12 weeks or earlier, will occur in March. * PROVE1 Publication Committee, for the study team.
Justpaul, a point I was making is that this Arm D trial, if Adam is accurate about it, is not going to be the VRTX's homerun strategy. It is conducted for a comparison purpose. The stats from it will be used as a reference point against which 12+12 and 12+36 data will be measured. Of course, I don't downplay the importance of the correlation between early (and sustained) response and SVR12 of the fast-responding group. By itself it doesn't have a pps moving value unless it is very good or very poor. The Arm D fast-responding group doesn't even have a control group to measure against.