Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Simeprevir · 11 trials · 8 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.
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 reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (\<LLOQ) (detectable or undetectable).
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.
| 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. |
| 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. |
| Simeprevir (TMC435) | EXPERIMENTAL | Treatment A: single oral dose of simeprevir (TMC435) 50 mg; and Treatment B: single oral dose of simeprevir (TMC435) 150 mg. A single 10 minute intravenous infusion of \[3H\]-TMC435 (100 microcurie) 100 microgram will be followed 5 hours later after administration of Treatment A and Treatment B in Period 1 and Period 2, respectively. |
| 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. |
| 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. |
| Ribavirin | DRUG | Participants will be administered 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) orally once daily up to 12 weeks. |
| 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. |
| Simeprevir (TMC435) | DRUG | Treatment A: Simeprevir (TMC435) 50 mg; and Treatment B: Simeprevir (TMC435) 150 mg; will be followed 5 hours later by a single 10 minute intravenous infusion of \[3H\]-TMC435 (100 microcurie) 100 microgram in Period 1 and Period 2, respectively. |
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 an investigational small molecule being developed for the treatment of chronic Hepatitis C virus infection, including genotypes 1 and 4. It is studied in combination with other antiviral agents such as sofosbuvir, with or without ribavirin, in patients with recurrent Hepatitis C post-liver transplant and in treatment-naive or experienced patients.
Simeprevir is being developed by Johnson & Johnson, traded on the New York Stock Exchange under the ticker JNJ. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with chronic Hepatitis C virus infection.
Simeprevir is in Phase 3 clinical development for chronic Hepatitis C virus infection. It has completed four clinical trials, including Phase 1, Phase 2, and Phase 3 studies, with a total enrollment of 413 participants. Simeprevir is investigational and not yet approved by regulatory authorities.
Simeprevir has completed four clinical trials. NCT01707342 assessed its bioavailability in healthy males. NCT02165189 studied it with sofosbuvir in recurrent genotype 1 Hepatitis C post-liver transplant. NCT02250807 and NCT02278419 evaluated it with sofosbuvir in chronic genotype 4 Hepatitis C infection.
Simeprevir is also known as TMC435. In clinical trials, the drug was administered as TMC435, and its pharmacokinetics were studied using both oral and intravenous forms of TMC435. This alternative name is used in research contexts to refer to the same compound.