Hepatitis C
Conditions
Brief summary
Prior trials have shown that many G1 CHC patients are ineligible or intolerant to pegylated (PEG)-based regimens due to prior severe side effects, worsening of cytopenias, exacerbation of underlying psychiatric disorders, or autoimmune disorders. These patients will not be candidates for treatment with the approvals of SMV and SOF in early 2014 due to the combination with PEG-regimens. Results of the COSMOS study suggest that these patients are likely to have excellent responses to SMV+SOF with or without RBV with 12 weeks of therapy, and that 24 weeks are unnecessary. This trial is designed to rapidly enroll and be completed in order to confirm this hypothesis.
Interventions
DRUGSimeprevir
DRUGSofosbuvir
DRUGRibavirin
Sponsors
Janssen, LP
SC Liver Research Consortium, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Targeted at least 20% enrollment of patients with cirrhosis 2. Adults \>/= age 18 years. 3. Active infection with hepatitis C virus (HCV) genotype 1 4. Must have health insurance that covers therapy with SOF+RBV 5. Female patients of childbearing age must have a negative pregnancy test prior to initiating therapy, use at least two effective methods of contraception during treatment, and undergo monthly pregnancy tests. 6. Patients must be either IFN-ineligible due to psychiatric, autoimmune, neurological, or other causes that are confirmed appropriate by the PI; OR, 7. IFN-intolerant due to flu-like symptoms, psychiatric problems, cytopenia or other causes deemed appropriate by the PI.
Exclusion criteria
1. Presence of HIV co-infection 2. Presence of hepatocellular carcinoma (HCC) 3. Prior organ transplantation 4. Any history of hepatic decompensation 5. Patients taking any of the following medications: * Anticonvulsants- Carbamazepine, Oxcarbazepine, Phenobarbital, or Phenytoin. * Anti-infectives-erythromycin, clarithromycin, or telithromycin. * Antifungals- systemic itraconazole, ketoconazole, posaconazole, fluconazole, or voriconazole. * Antimycobacterials- rifampin, rifabutin or rifapentine. * Corticosteroids- systemic dexamethasone. * Propulsives- Cisapride. * Herbals- Milk thistle or St. John's Wart. 6. Patients that have been exposed to direct acting anti-viral agents 7. Patients with severe renal impairment (estimated Glomerular Filtration Rate (eGFR) \<50 mL/min/1.73m2) or with end stage renal disease (ESRD). 8. Patients with platelet count \<50 x109/L, Hemoglobin \<10 g/dL, or Neutrophils \<0.5 x109/L. 9. Women who are pregnant. 10. Men whose partners are pregnant or plan on becoming pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Viral Response | 12 weeks | Comparison of sustained virologic response at 12 weeks post-treatment (SVR12) in 2 arms of IFN-II patients: one receiving 12 weeks of simeprevir (SMV) (150mg QD)+ sofosbuvir (SOF) (400mg QD) and the second receiving to SMV (150mg QD)+SOF (400mg QD)+weight-based ribavirin (RBV) 1000-1200 mg/day. SVR12 is defined as a patient having undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks post-treatment. Achieving SVR12 is generally indicative of hepatitis C infection being cured. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SMV+SOF IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD)
Simeprevir
Sofosbuvir | 14 |
| SMV+SOF+RBV IFN-II patients will receive 12 weeks of OLYSIO (Simeprevir) (150mg QD) + SOVALDI (Sofosbuvir) (400mg QD) + weight-based Ribavirin 1000-1200 mg/day
Simeprevir
Sofosbuvir
Ribavirin | 10 |
| Total | 24 |
Baseline characteristics
| Characteristic | SMV+SOF | SMV+SOF+RBV | Total |
|---|---|---|---|
| Age, Continuous | 50.84 years | 58.31 years | 53.95 years |
| BMI | 29.47 kg/m^2 | 27.56 kg/m^2 | 28.67 kg/m^2 |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 14 | 9 / 10 |
| serious Total, serious adverse events | 0 / 14 | 0 / 10 |
Outcome results
Primary
Sustained Viral Response
Comparison of sustained virologic response at 12 weeks post-treatment (SVR12) in 2 arms of IFN-II patients: one receiving 12 weeks of simeprevir (SMV) (150mg QD)+ sofosbuvir (SOF) (400mg QD) and the second receiving to SMV (150mg QD)+SOF (400mg QD)+weight-based ribavirin (RBV) 1000-1200 mg/day. SVR12 is defined as a patient having undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks post-treatment. Achieving SVR12 is generally indicative of hepatitis C infection being cured.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SMV+SOF | Sustained Viral Response | 13 Participants |
| SMV+SOF+RBV | Sustained Viral Response | 8 Participants |