Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ribavirin [Copegus], High ribavirin dose, Copegus, Ro 20-9963
ribavirin · 13 trials · 3 indications
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
SVR was defined as success if the participant had HCV RNA levels \<15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups A and B was reported in this analysis.
To investigate possible action mechanisms, three different models were fitted to viruskinetic data and evaluated using related log-likelihood function values. These models were designed assuming individual effects with respect to infectiousness (model 1), virus production (model 2) or degradation of infected cells rate (model 3). The following viruskinetic parameters were fitted in each model: initial viral load, loss rate of infected cells (delta), effectivity of interferon with respect to a pharmacokinetic-pharmacodynamic model. A lower log likelihood function value indicates a lesser fit for the model.
| Arm | Type | Description |
|---|---|---|
| Pegylated-interferon alfa-2a plus ribavirin | EXPERIMENTAL | Participants received pegylated-interferon alfa-2a 180 µg/week subcutaneously plus ribavirin 1000 mg/day orally for patients weighing \< 75 kg or 1200 mg/day for patients weighing ≥ 75 kg for 48 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | EXPERIMENTAL | Participants with HCV RNA levels greater than (\>) 15 international units per milliliter (IU/mL) at Week 4, HCV RNA greater than or equal to (\>=) 15 IU/mL at Week 8, and either HCV RNA less than (\<) 15 IU/mL or \>=2 times logarithmic (2 log10) drop at Week 12, will receive pegylated-interferon alfa-2a (Pegasys) 180 micrograms (mcg) subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 milligrams (mg) orally daily for 48 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | EXPERIMENTAL | Participants with HCV RNA levels \>15 IU/mL at Week 4, HCV RNA \>=15 IU/mL at Week 8, and either HCV RNA \<15 IU/mL or \>=2 log10 drop at Week 12, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 72 weeks, and ribavirin 1000 to 1400 mg orally daily for 72 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group C) | EXPERIMENTAL | Participants with HCV-RNA levels \>15 IU/mL at Week 4, and HCV-RNA \<15 IU/mL at Week 8, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 36 weeks, and ribavirin 1000 to 1400 mg orally daily for 36 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group D) | EXPERIMENTAL | Participants with HCV-RNA levels \>15 IU/mL at Week 4, and HCV-RNA \<15 IU/mL at Week 8, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | EXPERIMENTAL | Participants with HCV-RNA levels \<15 IU/mL at Week 4, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 24 weeks, and ribavirin 1000 to 1400 mg orally daily for 24 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | EXPERIMENTAL | Participants with HCV-RNA levels \<15 IU/mL at Week 4, will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. |
| Pegylated-interferon Alfa-2a + Ribavirin (Group NR) | EXPERIMENTAL | Participants who do not have any change in HCV-RNA levels at Weeks 4, 8, and 12 will not be randomized (NR) to any of the other groups. Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. |
| TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks) | EXPERIMENTAL | Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks). |
| TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks) | EXPERIMENTAL | Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). |
| TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks) | EXPERIMENTAL | Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). |
| TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks) | ACTIVE_COMPARATOR | Twelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). |
| Treatment Arm A | EXPERIMENTAL | 24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period. |
| Treatment Arm B | EXPERIMENTAL | 24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period. |
| Treatment Arm C (Control) | ACTIVE_COMPARATOR | 4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period. |
| Previous null responders (Cohort B): Group 4 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. |
| Previous null responders (Cohort B): Group 5 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 5 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. |
| Previous null responders (Cohort B): Group 6 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment. |
| Previous partial responders (Cohort A): Group 1 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 1 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. |
| Previous partial responders (Cohort A): Group 2 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. |
| Previous partial responders (Cohort A): Group 3 | EXPERIMENTAL | Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 3 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. |
| Group A | EXPERIMENTAL | Danoprevir 200 mg twice a day (BID) + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks |
| Group B | EXPERIMENTAL | Danoprevir 100 mg BID + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks |
| Group C | EXPERIMENTAL | Danoprevir 50 mg BID + ritonavir 100 mg + Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 24 weeks |
| Group D | EXPERIMENTAL | Danoprevir 100 mg BID + ritonavir 100 mg + Pegasys 180 μg sc qw + Copegus 1000 mg or 1200 mg po daily for 12 weeks or 24 weeks |
| Group E | ACTIVE_COMPARATOR | Pegasys 180 microgram sc qw + Copegus 1000 mg or 1200 mg po daily for 48 weeks |
| Part 1: Placebo | PLACEBO_COMPARATOR | Placebo in combination with standard doses of Pegasys and Copegus. |
| Part 1: RO5190591 300mg po | EXPERIMENTAL | RO5190591 300mg po every 8 hours in combination with standard doses of Pegasys and Copegus. |
| Part 1: RO5190591 600mg po | EXPERIMENTAL | RO5190591 600mg po every 12 hours in combination with standard doses of Pegasys and Copegus. |
| Part 1: RO5190591 900mg po | EXPERIMENTAL | RO5190591 900mg po every 12 hours in combination with standard doses of Pegasys and Copegus. |
| Part 2: Placebo | PLACEBO_COMPARATOR | If the safety and virological response data from Part 1 of the study are supportive, in Part 2 patients will be randomized to receive placebo in combination with standard doses of Pegasys and Copegus. |
| Part 2: RO5190591 300mg po | EXPERIMENTAL | If the safety and virological response data from Part 1 of the study are supportive, in Part 2 patients will be randomized to receive RO5190591 300mg po every 8 hours or 600mg po every 12 hours or 900mg po every 12 hours in combination with standard doses of Pegasys and Copegus. |
| Group 1 | EXPERIMENTAL | Group 1 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). |
| Group 2 | EXPERIMENTAL | Group 2 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (180 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). |
| Group 3 | EXPERIMENTAL | Group 3 will receive HCV polymerase inhibitor pro-drug 500mg po bid plus PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd for 24 weeks; after 24 weeks, those achieving a rapid virological response (RVR) will stop all medication, and non-RVR patients will remain on triple combination for an additional 24 weeks. |
| Group 4 | EXPERIMENTAL | Group 4 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). |
| Group 5 | EXPERIMENTAL | Group 5 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (1000 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). |
| Group 6 | EXPERIMENTAL | Group 6 will receive triple combination treatment with HCV polymerase inhibitor pro-drug (500 mg po bid) plus PEGASYS (90 micrograms sc weekly) plus Copegus (1000 or 1200mg po qd) for 24 weeks, followed by 24 weeks of open label Standard of Care (PEGASYS 180 micrograms sc weekly plus Copegus 1000/1200mg po qd). |
| Group 7 | ACTIVE_COMPARATOR | Standard of care (SOC) |
| A | EXPERIMENTAL | PegIFN-alpha 2a + RBV (commenced according to kidney function) adjusted to plasma levels. Treatment with erythropoetin 3x3,000IU/week up to 3x10,000IU/week in case of hemolytic anemia |
| B | ACTIVE_COMPARATOR | PegIFN-alpha 2a + RBV (weight based; 1,000 or 1,200 mg/day) |
| Pegylated Interferon (PEG-IFN) alfa-2a | EXPERIMENTAL | Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks. |
| Ribavirin | EXPERIMENTAL | Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks. |
| PEGASYS with COPEGUS | ACTIVE_COMPARATOR | - |
| RO5024048 1500mg in combination with PEGASYS | EXPERIMENTAL | - |
| RO5024048 3000mg in combination with PEGASYS | EXPERIMENTAL | - |
| RO5024048 in combination with PEGASYS and COPEGUS | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Pegylated-interferon alfa-2a | DRUG | Pegylated-interferon alfa-2a was administered subcutaneously once weekly. |
| Ribavirin | DRUG | Participants received ribavirin with food, as the bioavailability of ribavirin is increased when taken with food. Ribavirin was administered as split doses, that is, 2 doses were given 12 hours apart, 1 in the morning and 1 in the evening. Participants received either 1000 or 1200 mg ribavirin per day according to body weight: 400 mg (2 tablets) in the morning and 600 mg (3 tablets) in the evening for participants weighing \< 75 kg or 600 mg (3 tablets) in the morning and 600 mg (3 tablets) in the evening for participants weighing ≥ 75 kg. |
| pegylated interferon alpha2a | DRUG | - |
| Mericitabine | DRUG | Participants will receive mericitabine 1000 mg orally twice daily. |
| Peginterferon Alfa-2a | DRUG | Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly. |
| Placebo | DRUG | Participants will receive placebo matching to mericitabine orally twice daily. |
| Telaprevir | DRUG | Participants will receive telaprevir 750 mg orally three times daily. |
| Copegus | DRUG | total daily dose of 1000 mg or 1200 mg for 24 weeks |
| Pegasys | DRUG | 180 microgram subcutaneous once a week for 24 weeks |
| boceprevir | DRUG | 800 mg three times a day for 24 weeks |
| mericitabine placebo | DRUG | mericitabine placebo |
| boceprevir placebo | DRUG | boceprevir placebo |
| RO5024048 | DRUG | 1000 mg oral doses twice a day for 24 weeks |
| danoprevir | DRUG | 100 mg oral doses twice a day for 24 weeks |
| ritonavir | DRUG | 100 mg oral doses twice a day for 24 weeks |
| RO5190591 (Danoprevir) | DRUG | 300mg po q8h for 12 weeks |
| RO4588161 | DRUG | 1000mg po bid for 24 weeks |
| High ribavirin dose | DRUG | Ribavirin dose started according to kidney function (usually 1,800mg) and adapted according to plasma level during follow-up |
| Standard ribavirin dose | DRUG | Ribavirin dose started at 1,000mg (body weight \<65kg) or 1,200mg (body weight equal or \>65kg) |
| Pegylated Interferon (PEG-IFN) alfa-2a | DRUG | Pegylated interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy. |
| RO5024048 1500mg | DRUG | 1500mg po bid for 4 weeks |
| RO5024048 3000mg | DRUG | 3000mg po bid for 4 weeks |
Inclusion Criteria: * Adult patients, ≥ 18 years of age. * Chronic hepatitis C (CHC) patients with compensated liver disease (Child-Pugh A) who have participated in a donor protocol where access to treatment or re-treatment with PEGASYS monotherapy or in combination with Copegus was promised or dee...
Ribavirin is used to treat chronic hepatitis C, a viral infection of the liver. It is studied in combination regimens, including with pegylated interferon alfa-2a and direct-acting antivirals, in treatment-naive and previously treated patients. Trials have enrolled adults with hepatitis C genotype 1 and other chronic hepatitis C infections.
Ribavirin is a small molecule inhibitor of IMPDH1, inosine monophosphate dehydrogenase 1. By inhibiting this enzyme, ribavirin interferes with guanine nucleotide synthesis, which affects viral RNA replication. This mechanism underlies its activity against hepatitis C virus when used in combination antiviral regimens.
Ribavirin is developed by Roche Holding AG, which trades under the ticker RHHBY. Roche has sponsored clinical studies of ribavirin, including trials combining it with PEGASYS (pegylated interferon alfa-2a) and with other antivirals such as telaprevir and mericitabine in chronic hepatitis C.
Ribavirin has been studied in Phase 3 clinical development for chronic hepatitis C. Completed trials include a Phase 3 study of PEGASYS with or without ribavirin and several Phase 2 studies. No active trials are currently listed for ribavirin in this dataset.
Ribavirin has been evaluated in completed trials including NCT00800735, a Phase 3 study of PEGASYS with or without ribavirin; NCT02716779, a Phase 2 study of ribavirin in treatment-naive hepatitis C genotype 1 patients; NCT01482390, a Phase 2 combination study with mericitabine, telaprevir and peginterferon alfa-2a; and NCT00944684, a Phase 2 high-dose ribavirin study.
Yes, Copegus is a brand name for ribavirin. Ribavirin is also referred to as ribavirin [Copegus] and high ribavirin dose in some study contexts. These names refer to the same active ingredient used in chronic hepatitis C treatment.