Infection
Conditions
Keywords
Infection, Hepatitis C Genotype 1 Infection, Hepatitis C virus, HCV, Hepatocellular Carcinoma, HCC, Liver Transplantation, Pegylated Interferon Alfa 2a, PegIFN alfa-2a, Ribavirin, RBV, Telaprevir, Incivek, Antiviral drugs
Brief summary
The goal of this clinical research study is to learn if the antiviral combination of telaprevir, pegylated Interferon Alfa 2a (PegIFN alfa-2a) and ribavirin (RBV) can prevent the virus from coming back after the liver transplant. Telaprevir, PegIFN alfa-2a, and RBV are different antiviral drugs that work in combination at different stages of the HCV infection to stop the virus.
Detailed description
Study Drug Administration: If you are found to be eligible to take part in this study, you will take telaprevir 3 times a day. You will take RVB by mouth 2 times a day. You will receive PEGIFN alfa-2a by an injection under the skin 1 time a week. Study Visits: On the first day you take the study drug: * You will have an eye exam performed by the study doctor. * You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). * Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis virus. * You will be asked about any drugs you are taking or side effects you may be having. Every Week while you are on study: * You will have a physical exam, including measurement of your vital signs. * Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis C virus. If part of the blood sample is left over after the Hepatitis C testing, it will be stored in the laboratory as a back-up sample, in case the original samples get lost. This sample may also be used to check if the Hepatitis C virus has become resistant to the study drug. No extra blood will be drawn for this storage. * You will be asked about any drugs you are taking or side effects you may be having. * At Weeks 12, 24, 36, and 42, urine will be collected to check for infection and any other side effects to the drugs. If you can become pregnant, you will have a urine pregnancy test every 4 weeks Length of Treatment: You may continue receiving the antiviral therapy for up to 48 weeks, as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Follow-Up Visits: Beginning the day after you stop taking antiviral therapy (or the day of transplantation, whichever comes first), you will have up to 24 weeks of follow-up testing performed. About 4 and 20 weeks after your last dose: * You will have a physical exam, including measurement of your vital signs. * Blood (about 2 teaspoons) will be drawn for routine tests and to check for the hepatitis C virus. * You will be asked about any side effects you may be having. * At week 4 only, urine will be collected to check for infection and any other side effects to the drugs. This is an investigational study. Telaprevir, PegIFN alfa-2a, and RBV are all FDA approved and commercially available for the treatment of HCV infection. The use of these drugs in preventing the HCV infection is investigational. Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
Starting dose: 180 mcg subcutaneously once weekly.
DRUGRibavirin
Starting dose: 1,000 mg by mouth daily.
DRUGTelaprevir
Starting dose: 750 mg by mouth 3 times a day.
Sponsors
Vertex Pharmaceuticals Incorporated
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females aged ≥ 18 and ≤ 70 years 2. Detectable Hepatitis C Virus ribonucleic acid (HCV-RNA) in serum 3. HCV genotype 1 infection 4. Child-Pugh-Turcotte (CPT) score \< 7 and Model for End-Stage Liver Disease (MELD) score \< 18 5. PegIFN alfa-2a/RBV-naïve or previously treated patients (partial responders, null responders and relapsers) 6. Hepatocellular carcinoma within transplant criteria in the United Network for Organ Sharing (UNOS) Region IV: 1. Single lesion up to 6 cm, or 2. Two or three lesions with largest no greater than 5 cm and the total tumor diameter no greater than 9 cm 7. Listed for liver transplantation 8. Willingness to give written consent and agree to double contraception
Exclusion criteria
1. Decompensated cirrhosis 2. Baseline platelet count less than 35,000/µL 3. Baseline hemoglobin level less than 10 g/dL 4. Baseline absolute neutrophil count less than 750/mm3 5. Baseline creatinine clearance \< 50 mL per min. 6. Women with a positive pregnancy test at baseline or men whose female partners are pregnant or are contemplating pregnancy 7. Intolerance or contraindications to PegIFN alfa-2a/RBV use per standard treatment guidelines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Undetectable Viral Load 12 Weeks Post-transplant | 12 weeks post-transplant, up to 48 weeks for overall monitoring | The primary endpoint is number of participants with undetectable viral load at 12 weeks post-transplant (Post-transplant virological response, (PTVR)) which is defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) 12 weeks after liver transplantation). In order to have undetectable HCV RNA viral load after transplant, participants need to have undetectable viral load before the liver transplant. Response rate based on the modified intent-to-treat (ITT) population where ITT population is defined as those patients who have achieved an undetectable HCV-RNA level before the transplant. If patients drop out the study early due to severe toxicity or treatment failure including treatment-related death, they will be counted as non-responders when evaluating the response rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR) | 60 weeks | Sustained virological response (SVR) defined as a single undetectable HCV-RNA measurement 12 weeks after the 48-week treatment period for those still waiting for transplantation. The treatment duration will be summarized with descriptive statistics. Additional analyses based on evaluable patients also conducted regarding the PTVR response rate. The evaluable patients are defined as those patients who complete at least 16 weeks of treatment and have the 12 weeks post-transplant response measurement. The rate will also be computed stratified by the HCV treatment time (i.e., the 48-week HCV treatment versus less than 48 week HCV treatment) considering the different times under HCV. The SVR rate will be estimated, along with the exact 95% confident interval. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: April 2013 to February 2014. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment details
Study terminated early due to changes in research, alternate therapeutic treatment options.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon Alfa 2a + Ribavirin + Telaprevir Triple combination with Telaprevir, PegIFN alfa-2a and Ribavirin administered for 12 weeks, followed by dual therapy with PegIFN alfa-2a and Ribavirin. Dual therapy continued for 48 weeks of total duration of therapy, as standard of care treatment for cirrhotic patients, or until day of transplantation, whichever comes first. Starting doses for standard of care Pegylated Interferon (PegIFN) alfa-2a 180 mcg subcutaneously once weekly, for Ribavirin (RBV) 1,000 mg orally daily (\< 75 kg) and 1,200 mg orally daily (≥ 75 kg), and for Telaprevir 750 mg taken orally 3 times a day. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Pegylated Interferon Alfa 2a + Ribavirin + Telaprevir |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Number of Participants With Undetectable Viral Load 12 Weeks Post-transplant
The primary endpoint is number of participants with undetectable viral load at 12 weeks post-transplant (Post-transplant virological response, (PTVR)) which is defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) 12 weeks after liver transplantation). In order to have undetectable HCV RNA viral load after transplant, participants need to have undetectable viral load before the liver transplant. Response rate based on the modified intent-to-treat (ITT) population where ITT population is defined as those patients who have achieved an undetectable HCV-RNA level before the transplant. If patients drop out the study early due to severe toxicity or treatment failure including treatment-related death, they will be counted as non-responders when evaluating the response rate.
Time frame: 12 weeks post-transplant, up to 48 weeks for overall monitoring
Population: Study terminated early with one participant. No analysis possible.
Secondary
Sustained Virological Response (SVR)
Sustained virological response (SVR) defined as a single undetectable HCV-RNA measurement 12 weeks after the 48-week treatment period for those still waiting for transplantation. The treatment duration will be summarized with descriptive statistics. Additional analyses based on evaluable patients also conducted regarding the PTVR response rate. The evaluable patients are defined as those patients who complete at least 16 weeks of treatment and have the 12 weeks post-transplant response measurement. The rate will also be computed stratified by the HCV treatment time (i.e., the 48-week HCV treatment versus less than 48 week HCV treatment) considering the different times under HCV. The SVR rate will be estimated, along with the exact 95% confident interval.
Time frame: 60 weeks