Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the initiation of a Phase 3b study called OPTIMIZE that will evaluate twice-daily (BID) dosing of a telaprevir-based combination regimen in people chronically infected with genotype 1 hepatitis C virus (HCV) who have not been treated previously. This is the first Phase 3 study to evaluate twice-daily dosing of a protease inhibitor for the treatment of hepatitis C. OPTIMIZE will not include a control arm of pegylated-interferon and ribavirin alone.
“The sustained viral response rates, or viral cures, seen across a broad range of people in the Phase 3 studies of telaprevir set a high bar in the development of treatments for hepatitis C, and we are committed to studying new ways to further improve treatment”
"The sustained viral response rates, or viral cures, seen across a broad range of people in the Phase 3 studies of telaprevir set a high bar in the development of treatments for hepatitis C, and we are committed to studying new ways to further improve treatment," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "High viral cure rates were demonstrated in the Phase 2 study of twice-daily telaprevir and we're looking forward to conducting a larger study to confirm these findings."
The OPTIMIZE study will be conducted by Vertex's collaborator, Tibotec.
OPTIMIZE Study Design
In Vertex's recently completed Phase 3 registration program, patients who received telaprevir in combination with pegylated-interferon and ribavirin took telaprevir three times daily (750mg; every eight hours). OPTIMIZE is a randomized, open-label, Phase 3b study that will evaluate twice-daily dosing (BID) of telaprevir in people chronically infected with genotype 1 HCV who have not been treated previously. The study will be conducted globally at 135 clinical trial sites and enroll approximately 700 people. Patient screening for enrollment in the OPTIMIZE study is expected to start in November 2010.
For the first 12 weeks of the study, all patients will receive 2,250mg of telaprevir taken twice daily (1,125mg; BID) or three times daily (750mg; every eight hours) in combination with pegylated-interferon alpha-2a (PEGASYS®) and twice-daily ribavirin. Response guided therapy will be used to determine whether patients receive pegylated-interferon and ribavirin alone for an additional 12 weeks (24 weeks total) or 36 weeks (48 weeks total) based on their treatment response at week 4. The primary endpoint of the OPTIMIZE study is sustained viral response (SVR) 24 weeks after the end of all treatment. The primary objective is to demonstrate non-inferiority of BID telaprevir versus telaprevir dosed every eight hours as measured by SVR.
SVR data from the study are expected as early as 2012. If these data are positive, they may support the submission of a supplemental New Drug Application (sNDA) for twice-daily (BID) dosing of telaprevir.
Phase 2 C208 study
Study C208 was an exploratory, four-arm, randomized, open label, Phase 2 clinical trial that was conducted by Tibotec in Europe in 161 treatment-naïve patients with genotype 1 HCV infection. The objective of Study C208 was to explore the safety, efficacy, tolerability and pharmacokinetics of telaprevir administered every 12 hours (1,125mg) or every eight hours (750mg). Each dosing regimen of telaprevir was studied in combination with either PEGASYS® or PEGINTRON® and ribavirin, the currently approved therapies for chronic HCV infection.
Across the four arms, SVR rates were 82% and 83% in patients treated with telaprevir-based regimens every 12 hours (PEGINTRON and PEGASYS, respectively) and 81% and 85% in patients treated with the every 8-hour regimen (PEGINTRON and PEGASYS, respectively). The primary endpoint was SVR, and data from this study were presented at the 2009 annual meeting of the American Association for the Study of Liver Diseases (AASLD). The Phase 2 C208 data supported the initiation of the Phase 3b OPTIMIZE study.
In the C208 study, the frequency and severity of adverse events (AEs) and the rate of treatment discontinuations were similar to those reported in prior telaprevir trials. The rates of viral breakthrough were similar to the every 8- and every 12-hour regimens. The most common adverse events reported in patients in Study C208 were pruritis, nausea, rash, anemia, flu-like illness, fatigue and headache, and were similar overall between the patient groups receiving every 8-hour dosing and those receiving every 12-hour dosing.
Updates on the status of clinical trials of telaprevir are available online at www.clinicaltrials.gov.
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