Clinical Trials

Date: 2011-11-02

Type of information: Results

phase: 2b

Announcement: results

Company: Medivir (Sweden) Tibotec (J&J group)

Product: simeprevir (TMC435)

Action mechanism:

• direct-acting antiviral agent/protease inhibitor/RNA polymerase (NS3A) inhibitor. Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir.

Disease:

Therapeutic area: Infectious diseases

Country:

Trial details:

• The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The primary endpoint was proportion of patients with undetectable HCV RNA 24 weeks after the planned end of treatment (SVR24).The study includes patients who have relapsed, achieved partial response, or achieved no response (null responders) to PegIFN/RBV treatment. 62 percent (287/462) of patients had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4). Patients were equally randomized to one of seven different treatment arms, six TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with 48 weeks of PegIFN/RBV. The results are based on the intent-to-treat (ITT), population which included all randomized patients who took at least one dose of the study medication.

Latest news:

• • On November 2, 2011, data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared with those retreated with PegIFN and RBV alone. In this final analysis, all subgroups of treatment-experienced patients who failed previous PegIFN and RBV treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with PegIFN and RBV alone. Regardless of treatment duration all TMC435 treatment arms showed significantly improved effect on SVR24 versus PegIFN/RBV alone.
• Sustained Virological Response (SVR24) Rates in TMC435 Dose Groups (150 mg q.d.) vs Placebo; TMC435  (12PR48  N=66) relapsers SVR24 : 76.9 (20/26) ; Partial Responders SVR24 : 65.2 (15/23) ; Null Responders SVR24 :  52.9 (9/17) TMC435 (24PR48 N=68) relapsers SVR24 :  88.9 (24/27)  ; Partial Responders SVR24:  75.0 (18/24) ; Null Responders SVR24 :41.2 (7/17) TMC435 (48PR48  N=65 ) relapsers SVR24 :  88.5 (23/26 ; Partial Responders SVR24: 86.4 (19/22) ; Null Responders SVR24 : 58.8 (10/17 All TMC435  (PR48 N=199) relapsers SVR24 :  88.5 (23/26 ; Partial Responders SVR24: 75.3 (52/69)  ; Null Responders SVR24 :  51.0 (26/51) Placebo (PR48 N=66) relapsers SVR24 : 37.0 (10/27) ; Partial Responders SVR24 :8.7 (2/23) ; Null Responders SVR24 : 18.8 (3/16) q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment, SVR24: patients with undetectable HCV RNA (<25 IU/mL Undetectable) 24 weeks after planned EoT. All TMC435 groups: p<0.001 vs placebo. Prior Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of follow-up Prior Partial Responders: more than 2 log reduction in HCV RNA at W12 but not achieving undetectable at EoT Prior Null Responders: less than 2 log reduction in HCV RNA at W12 • On April 1, 2011, Medivir has announced that their partner, Tibotec has presented the results of a planned Week 24 interim analysis of the phase 2b ASPIRE study for TMC435 in treatment experienced hepatitis C patients in a late-breaker session at the 46th Annual meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany. In this Week 24 interim analysis, treatment-experienced patients who failed peginterferon and ribavarin treatment achieved significantly greater virologic response rates following treatment with TMC435-containing regimen at all doses, compared with placebo. Results demonstrated that the TMC435 150 mg dose group showed the highest response, particularly in prior null responders. In this 150 mg dose group, HCV RNA levels were undetectable at week 24 for between 82% and 91% of the patients. Results also showed that there was no statistically relevant difference in safety and tolerability between the TMC435 and placebo treated groups.

Is general: Yes