Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Simeprevir (SMV), Simeprevir (TMC435), TMC435
Simeprevir · 25 trials · 9 indications
SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable 12 weeks after actual EOT.
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (\<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment.
Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) lower limit of quantification (LLOQ; 25 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the actual end of study drug treatment.
Participants are considered to have reached SVR12 if at the actual end of treatment hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 25 IU/mL undetectable, AND at the time point of SVR12 (i.e., 12 weeks after the planned end of treatment \[EOT\]), HCV RNA levels \< 25 IU/mL undetectable.
Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) lower limit of quantification (LLOQ; 25 international unit per milliliter \[IU/mL\]) undetectable at end of treatment and, 2). the HCV RNA is \< LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.
The primary objective is to evaluate the efficacy of TMC435 in combination with pegylated interferon alpha-2a (PegIFNα 2a)/ribavirin (RBV) with respect to the proportion of participants with chronic HCV-4 infection achieving SVR 12 weeks after planned end of treatment (SVR12) in the overall population as well as in the different subpopulations (treatment-naïve, previous relapsers and previous non-responders).
Participants are considered to have reached SVR12 if both conditions below are met: 1) HCV RNA levels less than (\<) 25 International unit per milliliter (IU/mL) undetectable; 2) HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable.
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual end of treatment (EOT), and HCV RNA levels \<25 IU/mL undetectable or HCV RNA levels \<25 IU/mL detectable at 12 Weeks after end of treatment.
The table below shows the percentage of participants in each treatment group with an SVR12 defined as participants with undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma HCV RNA 12 weeks after the last dose of treatment (Week 36 or 60). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with a SVR24 defined as participants with undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment and at 24 weeks after the last dose of treatment (Week 48 or 72). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with undetectable HCV RNA less than 1.2 log10 IU/mL during treatment and at end of treatment (EOT). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period. Viral breakthrough is defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of greater than 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the number of participants in each treatment group who demonstrated viral relapse, defined as having undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at end of treatment (EOT \[Week 24 or 48\]) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of an assessment of sustained virologic response (SVR). The number of participants analyzed in each treatment group below are those with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the number of participants in each treatment group with abnormal ALT levels at Baseline who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at EOT. At Baseline, 15 treatment-naïve participants, 13 prior relapsers, and 13 prior non-responders had abnormal ALT levels at Baseline. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with greater than or equal to 2 log10 IU/mL drop from baseline in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at each time point during treatment and post-treatment follow-up. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid \[HCV RNA\] \<1.2 log10 IU/mL detectable/undetectable at Week 4 and \<1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2b and RBV at Week 24. Participants in the TMC435 Treatment-Naïve and TMC435 Prior Relapser treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48 (does not apply to the TMC435 Non-responder treatment group because the specified treatment duration was 48 weeks and RGT criteria was not assessed at Week 24). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the median (range) AUC24h values for TMC435 for all participants in each TMC435 treatment group who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the median (range) TMC435 predose plasma concentrations (C0h) and maximum concentration (Cmax) values for participants in each treatment group. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).
The Cmin is the minimum observed plasma concentration.
The Cmax is the maximum observed plasma concentration.
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
The Cmin is the minimum observed plasma concentration.
The Cmax is the maximum observed plasma concentration.
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]) detectable or undetectable at 12 weeks after the end of study drug treatment.
SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (\<) lower limit of quantification (LLOQ; 15 international unit per milliliter \[IU/mL\]), detectable or undetectable at 12 weeks after EOT.
Participants will be considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) 15 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the end of treatment. End of treatment is at Week 12 (for Arms 1 and 2) or Week 24 (for Arm 3); therefore, outcome will be measured at Week 24 (for Arms 1 and 2) or Week 36 (for Arm 3).
Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (\<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (\<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the planned end of treatment.
The table below shows the least-squares (LS) mean change and 95% confidence intervals (CI) change from baseline at Week 4 in HCV RNA levels for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg). The statistical analyses show the difference in LS mean change from baseline from the PR48 control group and the 95% CI for each dose group (ie, each TMC435 dose group minus PR48 control). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with undetectable plasma HCV RNA levels at Weeks 4, 12, 24, 48, and end of treatment (EOT, up to Week 24 or 48). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed."NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with a decrease of greater than (\>) or equal (=) to 2 log10 IU/mL from baseline in plasma HCV RNA levels at time points during the treatment period and post treatment follow-up period. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group with plasma HCV RNA levels undetectable or below the limit of quantification (\<1.2 log10 IU/mL detectable ) at time points during treatment and post treatment follow-up.The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants in each treatment group who experienced viral relapse within 12 weeks (ie, at Week 36 or 60) after actual end of treatment (EOT) (up to Week 24 or 48). Viral relapse was defined as confirmed detectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels during the post treatment follow-up period at Weeks 36 or 60 in participants with undetectable plasma HCV RNA at EOT. The statistical analysis shows the difference in treatments (ie, each TMC435 group minus PR48 control) in viral relapse. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the mean (standard deviation) of the actual HCV RNA values by treatment group at Baseline and Weeks 4, 12, 24, 48, end of treatment (EOT, up to Weeks 24 or 48), Weeks 60 and 72 (Week 24 in the post-treatment follow-up period). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the number of participants whose ALT results were within the normal range on Day 1 (initial day of treatment), Week 24, 48, and EOT (up to Weeks 24 or 48).The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the percentage of participants with a SVR4, SVR12, and SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT) (up to Weeks 24 or 48) and at 4, 12, and 24 weeks, respectively, after the last dose of treatment. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the mean (standard deviation) predose plasma concentration (C0h) for participants in each treatment group at Weeks 4, 12, and 24. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the mean predose plasma concentration (C0h) for participants in the 2 TMC435 50 mg treatment groups combined and for participants in the 2 TMC435 100 mg treatment groups combined who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the mean AUC24 of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the median time in hours to reach the maximum plasma concentration (tmax) of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
The table below shows the number of participants who met response-guided treatment (RGT) stopping criteria in the TMC435 treatment groups. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than 1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20 were to stop all study medication (TMC435, PegIFNα-2a, and ribavirin) at Week 24. All other participants continued PegIFNα-2a and ribavirin until Week 48. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).
| Arm | Type | Description |
|---|---|---|
| Simeprevir and Sofosbuvir | EXPERIMENTAL | Subjects will receive oral capsule of Simeprevir 150 milligram (mg) along with oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12. |
| Arm 1 (Simeprevir/Sofosbuvir) | EXPERIMENTAL | 100 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. |
| Arm 2 (Simeprevir/Sofosbuvir) | EXPERIMENTAL | 150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks. |
| TMC435 + PegIFNα-2a + RBV | EXPERIMENTAL | TMC435 will be administered as triple therapy with pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV). |
| TMC435 150 mg | EXPERIMENTAL | Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. |
| TMC435 100 mg | EXPERIMENTAL | Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. |
| Control | PLACEBO_COMPARATOR | Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks. |
| TMC435 | EXPERIMENTAL | - |
| TMC435/PR | EXPERIMENTAL | - |
| TVR/PR | ACTIVE_COMPARATOR | - |
| TMC435 + pegylated interferon alpha-2a + ribavirin | EXPERIMENTAL | Patients will be administered TMC435 150 mg along with pegylated interferon alpha-2a 180 microgram and ribavirin 1000 or 1200 mg for 12 weeks. Pegylated interferon alpha-2a and ribavirin will only be continued until 24 to 48 weeks. |
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | EXPERIMENTAL | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48. |
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | EXPERIMENTAL | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48. |
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | EXPERIMENTAL | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
| Placebo | PLACEBO_COMPARATOR | Placebo 150 mg capsule once daily for 12 weeks in addition peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 48 weeks |
| TMC435 100 mg 12 Wks + PR24/48 | EXPERIMENTAL | Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48. |
| TMC435 100 mg 24 Wks + PR24/48 | EXPERIMENTAL | Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment will be stopped at Week 24 if participants achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \< 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48. |
| TMC435 100 mg 12 Wks + PR 24/48 | EXPERIMENTAL | Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 for participants who achieved HCV RNA \< 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48. |
| PBO 12 Wks + PR 48 | EXPERIMENTAL | Participants received placebo (PBO) once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
| Panel 1 | EXPERIMENTAL | Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70. |
| Panel 2 | EXPERIMENTAL | Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56. |
| Simeprevir + Daclatasvir | EXPERIMENTAL | Participants who have Hepatitis C virus (HCV) genotype 1b infection with advanced fibrosis or compensated cirrhosis (METAVIR F3/F4) will receive simeprevir 150 milligram (mg) capsule and daclatasvir 60 mg tablet orally once daily for 12 or 24 weeks. |
| Arm A | EXPERIMENTAL | Chronic hepatitis C virus (HCV) genotype 1 infected participants with early stages of liver fibrosis, will receive Simeprevir (SMV) 150 milligram (mg), Daclatasvir (DCV) 60 mg and Sofosbuvir (SOF) 400 mg once daily for 6 weeks. |
| Arm B | EXPERIMENTAL | Chronic HCV genotype 1 infected participants with cirrhosis, will receive SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. |
| Group A1 | EXPERIMENTAL | Participants without cirrhosis will receive simeprevir 150 milligram (mg) capsule along with sofosbuvir 400 mg tablet, orally, once daily for 8 weeks. |
| Group A2 | EXPERIMENTAL | Participants without cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks. |
| Group B | EXPERIMENTAL | Participants with cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks. |
| Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1) | EXPERIMENTAL | Participants will be administered simeprevir capsule 150 milligram (mg), sofosbuvir 400 mg tablet, and ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram \[kg\]) or 3 x 200 mg tablets (for participants weighing more than 75 kg weight), orally once daily up to 12 weeks. |
| Simeprevir plus Sofosbuvir (Arm 2) | EXPERIMENTAL | Participants will be administered simeprevir capsule 150 mg and sofosbuvir 400 mg tablet orally once daily up to 12 weeks. |
| Simeprevir plus Sofosbuvir (Arm 3) | EXPERIMENTAL | Participants will be administered simeprevir 150 mg capsule and sofosbuvir 400 mg tablet orally once daily 24 weeks. |
| Part 1 | EXPERIMENTAL | Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy. |
| Part 2 | EXPERIMENTAL | Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy. |
| Arm 1 | EXPERIMENTAL | 30 patients will receive TMC435 (150 mg once a day) plus PSI-7977(GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 24 weeks and followed by a 24-week follow-up phase. |
| Arm 2 | EXPERIMENTAL | 15 patients wiil receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 24 weeks of and followed by a 24-week follow-up phase. |
| Arm 3 | EXPERIMENTAL | 30 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 12 weeks and followed by a 36-week follow-up phase. |
| Arm 4 | EXPERIMENTAL | 15 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 12 weeks and followed by a 36-week follow-up phase. |
| TMC12/PR24 50 mg | EXPERIMENTAL | Participants received TMC435 50 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24 Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48. |
| TMC12/PR24 100 mg | EXPERIMENTAL | Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48. |
| TMC24/PR24 50 mg | EXPERIMENTAL | Participants received TMC435 50 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435, PR) at Week 24. All other participants continued PR until Week 48. |
| TMC24/PR24 100 mg | EXPERIMENTAL | Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48. |
| PR48 Control | EXPERIMENTAL | Participants received PegIFNa-2a and ribavirin (PR) for 48 weeks (PR48 control group) |
| Name | Type | Description |
|---|---|---|
| Simeprevir | DRUG | Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12. |
| Sofosbuvir | DRUG | Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12. |
| TMC435 | DRUG | 150 mg taken orally (by mouth) as a capsule with food once daily for 12 weeks. |
| Pegylated interferon alfa-2a (PegIFNα-2a) | DRUG | 180 mcg administered according to the manufacturer's prescribing information as a 0.5 mL subcutaneous (under the skin) (SC) injection once a week in the morning or evening for up to 24 weeks. |
| Ribavirin (RBV) | DRUG | 1000 mg or 1200 mg administered according to the manufacturer's prescribing information for up to 24 weeks. If the participant's baseline body weight is \< 75 kg, the total daily dose of RBV will be 1000 mg, administered orally (by mouth) as 400 mg (2 tablets of 200 mg, intake with food) in the morning and 600 mg (3 tablets of 200 mg, intake with food) in the evening. If the baseline body weight is \> or = 75 kg, the total daily dose will be 1200 mg, administered as 600 mg in the morning and evening (3 tablets of 200 mg per intake, with food). |
| Peginterferon-alpha (PegIFNα-2a) | DRUG | PegIFNα-2a (180 micrograms \[μg\] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks. |
| Placebo | DRUG | Matching placebo capsules taken orally with food once-daily for 48 weeks. |
| TVR | DRUG | TVR Type=exact number, unit=mg, number=375, form=tablet, route=oral use. TMC435 placebo Form=capsule, route=oral use. 2 TVR tablets are taken 3 times a day together with 150 mg TMC435 placebo capsule once daily for 12 weeks, in addition to peginterferon alfa-2a and ribavirin for 48 weeks |
| Pegylated interferon alpha-2a | DRUG | Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks. |
| Ribavirin | DRUG | Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks. |
| Peginterferon alfa-2b (pegIFN alfa-2b) | DRUG | PegIFN alfa-2b will be supplied as a vial containing dried and frozen powder with 74,148 or 222 mcg pegIFN alpha-2b attached to 0.7 ml injection water (50, 100 or 150 mcg/0.5mL pegIFN alpha-2b) and will be administered according to the manufacturer's prescribing information as 1.5 mcg/kg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks. |
| Peginterferon alpha-2a or Peginterferon alpha-2b (PegIFNα-2a/b) | DRUG | One subcutaneous (under the skin) injection of PegIFNα-2a (containing 0.5 mL solution with 180 mcg PegIFNα-2a) OR PegIFNα-2b (0.5 mL from a pre-filled pen) once weekly for up to 48 weeks. |
| Peginterferon alpha-2a (PegIFN alpha-2a) | DRUG | One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks. |
| Peginterferon alfa-2a (PegIFNα-2a ) | DRUG | PegIFNα-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks. |
| Peginterferon alfa-2a (pegIFN alfa-2a) | DRUG | PegIFN alfa-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks for patients randomized to TMC435 and for up to 48 weeks for patients randomized to placebo. |
| Pegylated interferon (pegIFN alpha-2a) | DRUG | 180 mcg injected subcutaneously (by a syringe under the skin) once weekly for 12 to 36 weeks (or until Week 48). |
| Simeprevir (SMV) | DRUG | Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2. |
| Ledipasvir (LDV) | DRUG | Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2. |
| Sofosbuvir (SOF) | DRUG | Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2. |
| Daclatasvir | DRUG | Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks. |
| Simeprevir 150 mg | DRUG | Simeprevir 150 mg capsule orally once daily. |
| Daclatasvir 60 mg | DRUG | Daclatasvir 60 mg tablet orally once daily. |
| Sofosbuvir 400 mg | DRUG | Sofosbuvir 400 mg tablet orally once daily. |
| Cyclosporine | DRUG | Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks. |
| Tacrolimus | DRUG | Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks. |
| PSI-7977 (GS7977) | DRUG | PSI-7977 (GS7977) will be administered as oral tablets (2 tablets of 200 mg for Cohort 1 and 1 tablet of 400 mg for Cohort 2) once a day. |
| PegIFNα-2a | DRUG | One subcutaneous injection of PegIFNα-2a 180 μg once weekly for 12, 24, or 48 weeks. |
| RBV | DRUG | 300, 400, or 500-mg tablets orally twice daily for 12, 24, or 48 weeks. |
Inclusion Criteria: * Subjects with confirmed hepatitis C virus (HCV) with HCV RNA greater than (\>) 10000 international unit per milliliter (IU/mL) * Subjects who are treatment naive or treatment-experienced. * Subjects must have documentation of a liver biopsy or fibroscan or agree to have one du...
Simeprevir is used to treat chronic hepatitis C virus infection, including genotype 1 and genotype 4 hepatitis C. It is studied in treatment-naive and treatment-experienced adults, often in combination with other direct-acting antivirals such as sofosbuvir, daclatasvir, and ledipasvir, rather than as a standalone therapy.
Simeprevir is developed by Johnson & Johnson, which trades under the ticker JNJ. The company has sponsored the clinical trial program evaluating simeprevir in chronic hepatitis C, including studies combining it with sofosbuvir, daclatasvir, and ledipasvir in genotype 1 and genotype 4 infections.
Simeprevir is in Phase 3 development for chronic hepatitis C. The trial program includes completed Phase 2 studies of combination regimens, and the drug remains an investigational agent in clinical development rather than a newly approved therapy in this dataset.
Simeprevir has been studied in five completed trials, including NCT02421211, which tested pharmacokinetic interactions with ledipasvir in a simeprevir, sofosbuvir, and ledipasvir regimen, and NCT02349048, NCT02278419, and NCT02268864, which evaluated combinations with daclatasvir or sofosbuvir in chronic hepatitis C.
Yes. Simeprevir is also known as SMV, TMC435, and simeprevir 150 mg. These are alternative names and dose designations for the same small-molecule hepatitis C drug developed by Johnson & Johnson, so searches for any of these terms refer to the same compound.