Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TMC647055 · 3 trials · 3 indications
SVR12 is defined as undetectable HCV RNA at the actual end of treatment and HCV RNA less than 25 IU/mL at 12 Weeks after the actual end of treatment.
Number of patients with adverse events, serious adverse events, abnormal changes in safety related laboratory values, abnormal changes in vital signs and physical examination, and abnormal echocardiogram.
Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg
Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg
Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg
Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg
AUC from time 0 up to 24 hours after dosing, from time 0 to the time of the last measurable concentration, and from time 0 to infinite time will be assessed. Assessment will be following single oral doses of TMC647055/Ritonavir 150/30 mg, 450/30 mg and 600/30 mg
Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone
Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone
AUC from time 0 up to 24 hours after dosing will be assessed. Assessment will be following TMC435 75 mg co-administered with TMC647055/ritonavir 450/30 mg; TMC435 100 mg co-administered with TMC647055/ritonavir 600/30 mg; and TMC435 150 mg alone
Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg
Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg
AUC from time 0 up to 24 hours after dosing will be assessed. Assessment will be following TMC647055 600 mg co-administered with TMC435 100 mg and ritonavir 30 mg; and TMC647055 450 mg co-administered with TMC435 75 mg and ritonavir 30 mg
| Arm | Type | Description |
|---|---|---|
| Panel 1 | EXPERIMENTAL | 10 chronic HCV genotype 1a (GT1a) infected treatment-naive patients/prior relapsers who will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose ritonavir and ribavirin. |
| Panel 2 Arm 1 | EXPERIMENTAL | 10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir and ribavirin. |
| Panel 2 Arm 2 | EXPERIMENTAL | 10 chronic HCV GT1b infected treatment-naive patients/ prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir. |
| Panel 3 - Arm 1 | EXPERIMENTAL | 8 chronic HCV GT1a infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir + ribavirin. |
| Panel 3 - Arm 2 | EXPERIMENTAL | 8 chronically HCV GT1b infected treatment naïve patients/prior relapsers will receive TMC435 + TMC647055 + low-dose ritonavir. |
| Panel 4 - Arm 1 | EXPERIMENTAL | 20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (30 mg once daily) |
| Panel 4 - Arm 2 | EXPERIMENTAL | 20 chronic HCV GT1a or GT1b infected treatment-naive patients/ prior relapsers will receive 12 weeks of treatment with TMC435 + TMC647055 + low-dose RTV + GSK2336805 (60 mg once daily) |
| TMC647055 150 mg or placebo + ritonavir (RTV) | EXPERIMENTAL | Participants in Part 1 will receive a single oral dose of 150 mg of TMC647055 or placebo with 30 mg of RTV on Day 1. |
| TMC647055 450 mg or placebo + RTV | EXPERIMENTAL | Participants in Part 1 will receive a single oral dose of 450 mg of TMC647055 or placebo with 30 mg of RTV on Day 1. |
| TMC647055 600 mg or placebo + RTV | EXPERIMENTAL | Participants in Part 1 will receive a single oral dose of 600 mg of TMC647055 or placebo with 30 mg of RTV on Day 1. |
| Sequence 1 (Treatment A-B-C) | EXPERIMENTAL | Participants in Part 2 will receive Treatment ABC in the following sequence - Treatment A: TMC435 150 mg once daily on Days 1 to 7; Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Sequence 2 (Treatment B-C-A) | EXPERIMENTAL | Participants in Part 2 will receive Treatment BCA in the following sequence - Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment A: TMC435 150 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Sequence 3 (Treatment C-A-B) | EXPERIMENTAL | Participants in Part 2 will receive Treatment CAB in the following sequence - Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment A: TMC435 150 mg once daily on Days 1 to 7; and Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Sequence 4 (Treatment A-C-B) | EXPERIMENTAL | Participants in Part 2 will receive Treatment ACB in the following sequence - Treatment A: TMC435 150 mg once daily on Days 1 to 7; Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Sequence 5 (Treatment B-A-C) | EXPERIMENTAL | Participants in Part 2 will receive Treatment BAC in the following sequence - Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment A: TMC435 150 mg once daily on Days 1 to 7; and Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Sequence 6 (Treatment C-B-A) | EXPERIMENTAL | Participants in Part 2 will receive Treatment CBA in the following sequence - Treatment C: TMC435 100 mg once daily + TMC647055 600 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; Treatment B: TMC435 75 mg once daily + TMC647055 450 mg once daily in combination with RTV 30 mg once daily on Days 1 to 7; and Treatment A: TMC435 150 mg once daily on Days 1 to 7 with a washout period of 7 days between consecutive treatment sessions in each individual participant. |
| Panel 2 | EXPERIMENTAL | TMC647055 in combination with TVR for 10 or 14 days. Immediately followed by the extension phase: TVR at a dose of 750 mg every 8 hours for 12 weeks in combination with Peg IFN and RBV followed by either 12 or 36 weeks of PegIFN -RBV treatment alone. |
| Name | Type | Description |
|---|---|---|
| TMC647055 | DRUG | Type=exact number, unit=mg, number=150, form=capsule, route=oral. 3 or 4 capsules of 150 mg will be administered once daily. |
| TMC435 | DRUG | Type=exact number, unit=mg, number=75, form=capsule, route=oral. 1 capsule of 75 mg will be administered once daily. |
| Ritonavir | DRUG | Type=exact number, unit=mg, number=30 or 50, form=tablet or solution, route=oral. 0.375 mL or 0.625 ml (80 mg/mL) solution will be administered once daily. |
| Ribavirin | DRUG | Type=exact number, unit=mg, number=200, form=tablet, route=oral. 5 to 6 (1000 or 1200 mg) tablets will be administered once daily, divided in 2 daily doses. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment 5 or 6 (depending on bodyweight) tablets of ribavirin (equivalent to 200 mg/tablet) per day, divided in 2 daily doses for an additional 12 or 36 weeks. |
| Pegylated interferon alpha-2a (PegIFN) | DRUG | Type=exact number, unit=mcg, number=180, form=solution, route=subcutaneous injection. PegIFN 0.5 mL prefilled syringe equivalent to 180 mcg will be administered as a subcutaneous (under the skin) injection as follow-up (FU) treatment for 12 or 36 weeks based on follow-up treatment principles as described in the protocol. Patients meeting the Follow-UP (FU) treatment criteria specified in the protocol will receive treatment with Pegylated interferon alpha-2a (PegIFN) 0.5 mL prefilled syringe equivalent to 180 mcg administered as a subcutaneous (under the skin) injection for an additional 12 or 36 weeks. |
| GSK2336805 | DRUG | Type=exact number, unit=mg, number=30 or 60, form=tablet, route=subcutaneous injection. GSK2336805 one or two 30 mg tablet(s) taken orally (by mouth) once daily for 12 weeks. |
| Placebo | DRUG | Placebo capsule once daily taken orally on Day 1 in Part 1 |
| Ritonavir (RTV) | DRUG | RTV 30 mg (ie, 0.38 mL oral solution of RTV \[80 mg/mL strength\]) taken orally on Day 1 in Part 1 and on Days 1 to 7 in Part 2 |
| TVR | DRUG | type=exact number, unit= mg, number=1125, form=tablet, route=oral use. TVR is to be taken twice daily at a dose of 1125 mg for 10 days. |
| PegFN | DRUG | type= exact number, unit= mcg, number=180, form=solution, route=subcutaneous. PegIFN is to be injected once per week for 24 or 48 weeks. |
| RBV | DRUG | type=exact number, unit=mg, number=1000 or 1200, form=tablet, route=oral use. RBV is to be taken at 1000 or 1200 mg per day in 2 divided doses, depending on the weight for 24 or 48 weeks. |
Inclusion Criteria: * Documented chronic genotype 1a or genotype 1b hepatitis C virus (HCV) infection with HCV ribonucleic acid (RNA) level \>100,000 IU/mL at screening * Treatment-naive or documented prior relapser to previous treatment regimens and has stopped treatment at least 3 months before s...
TMC647055 is an investigational small molecule being studied for the treatment of Hepatitis C, including chronic genotype 1 Hepatitis C virus infection. It has been evaluated in clinical trials in patients with Hepatitis C and chronic Hepatitis C, as well as in healthy volunteers for pharmacokinetic studies.
TMC647055 is being developed by Johnson & Johnson (NYSE: JNJ). The company has sponsored clinical trials of the drug in combination with other antiviral agents for Hepatitis C.
TMC647055 has completed Phase 2 clinical development. A Phase 2 trial (NCT01724086) evaluated a 12-week combination therapy of TMC647055 with TMC435, with or without GSK23336805 and a pharmacokinetic enhancer, with or without ribavirin, in patients with chronic genotype 1 Hepatitis C.
TMC647055 has been studied in three completed clinical trials: NCT01582035, a Phase 1 study of multiple doses in combination with telaprevir in Hepatitis C patients; NCT01724086, a Phase 2 study in chronic Hepatitis C patients; and NCT02064842, a Phase 1 study in healthy Japanese participants.
TMC647055 is not FDA approved. It is an investigational drug that has completed clinical trials, including Phase 2 studies, but it remains in clinical development and has not been approved for any use.
TMC647055 is a small molecule antiviral agent. While its specific molecular target has not been disclosed, it is being studied in combination with other direct-acting antivirals such as TMC435 (simeprevir) and telaprevir for the treatment of Hepatitis C.