A Phase 2a Study to Evaluate Viral Kinetics and Safety of Telaprevir in Participants With Genotype 2 or 3 Hepatitis C Infection
- Conditions
- Hepatitis C, Chronic
- Interventions
- Registration Number
- NCT00561015
- Lead Sponsor
- Tibotec BVBA
- Brief Summary
The purpose of this study is to assess the effect of telaprevir on early hepatitis (inflammation of the liver) C virus (HCV) viral kinetics in treatment-naive participants who are chronically (lasting a long time) infected with genotype 2 or 3 HCV.
- Detailed Description
This is a Phase 2a multicenter (when more than one hospital or medical school team work on a medical research study), partially blinded, randomized (study drug assigned by chance) stratified (arrange in groups for analysis of results e.g., stratify by age, sex, etc.) for genotype, multiple dose study. The trial will consist of Screening period (6 weeks), Treatment period (24 or 26 weeks) and Follow-up period (24 weeks). The Treatment period will include 2 weeks investigational treatment phase and a 24 week standard treatment phase. All the eligible participants who were never treated for HCV will be enrolled for the trial and will receive the investigational treatment regimen to which they have been randomly assigned for 2 weeks. After this in the standard treatment phase participants will receive the standard treatment of care consisting of pegylated interferon (Peg-IFN)-alfa-2a 180 microgram once weekly and ribavirin (RBV) 400 milligram twice per day. Efficacy will primarily be evaluated by HCV viral load quantification. Participant's safety will be monitored throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- Participants chronically infected with genotype 2 or 3 hepatitis C virus (HCV) with amount of virus in the blood greater than 10,000 international units per milliliter (IU/ml)
- Participants who were never treated for hepatitis C virus infection
- Participants without any significant lab abnormalities
- Participants who agree to the use of two effective methods of contraception
- Participant who were judged to be in good health
- Participants who had contraindications for starting anti-HCV therapy
- Participants who had history or evidence of liver cirrhosis (serious liver disorder in which connective tissue replaces normal liver tissue, and liver failure often occurs) or decompensated liver disease or hepatocellular carcinoma (type of cancer)
- Participant infected with human immunodeficiency virus (a life-threatening infection that you can get from an infected person's blood or from having sex with an infected person) or hepatitis B virus
- Females who are pregnant (carrying an unborn baby), planning to be pregnant or breastfeeding
- Participants who have hypersensitivity to tartrazine
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for chronic hepatitis C (inflammation of the liver) genotype 2 will receive telaprevir (TVR) 750 milligram (mg) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) from Day 15 to Week 26 (standard treatment phase). Each dose of pegylated interferon 180 microgram (mcg) will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks. TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for CHC genotype 2 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 2 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for CHC genotype 2 will receive TVR matching placebo (Pbo) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 2 Placebo Participants who are never treated for CHC genotype 2 will receive TVR matching placebo (Pbo) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 3 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for CHC genotype 3 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of Peg-IFN-alfa-2a and RBV from Day 15 to Week 26 (standard treatment phase). Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks. TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 3 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for CHC genotype 3 received TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 3 Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) Participants who are never treated for CHC genotype 3 will receive TVR matching Pbo tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 3 Placebo Participants who are never treated for CHC genotype 3 will receive TVR matching Pbo tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2 Telaprevir Participants who are never treated for chronic hepatitis C (inflammation of the liver) genotype 2 will receive telaprevir (TVR) 750 milligram (mg) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) from Day 15 to Week 26 (standard treatment phase). Each dose of pegylated interferon 180 microgram (mcg) will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks. TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2 Telaprevir Participants who are never treated for CHC genotype 2 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks. TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 3 Telaprevir Participants who are never treated for CHC genotype 3 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of Peg-IFN-alfa-2a and RBV from Day 15 to Week 26 (standard treatment phase). Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks. TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 3 Telaprevir Participants who are never treated for CHC genotype 3 received TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Day 15 Baseline, Pre-dose (Day 15) Level of HCV RNA in plasma was measured using COBAS TaqMan HCV test v2.0 (an in vitro nucleic acid amplification test for quantitation of HCV RNA genotypes 1 through 6 in human serum or plasma, using the COBAS AmpliPrep Total Nucleic Acid Isolation Kit (TNAI) for preparation of highly purified total nucleic acid from serum or plasma and automated amplification and detection on TaqMan 48 Analyzer). Lower limit of quantification was 25 international units/milliliter (IU/ml) and limit of detection was 10 IU/ml. Assay used was reverse transcription-polymerase chain reaction (RT-PCR) methodology.
Maximum Plasma Concentration (Cmax) for Telaprevir on Day 1 Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hour [hr]) The Cmax is defined as the maximum observed analyte concentration. The Cmax was measured in nanogram/milliliter (ng/ml).
Time to Reach Maximum Plasma Concentration (Tmax) for Telaprevir on Day 1 Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr) The Tmax is defined as the actual sampling time to reach maximum observed analyte concentration. The analyte concentration associated with Tmax is referred to as Cmax.
Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 1 Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr) The AUC is defined as area under the plasma concentration-time curve over the dosing interval (8 hr), calculated by the lin-up/ log-down method.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Virological Response (HCV RNA Level < 10 IU/ml) Baseline, Day 12, 15, Week 4, 6, 14 and EOT (Week 24/26 or early discontinuation) Virological response was defined as having HCV RNA level less than a particular threshold that is less than 10 IU/ml (undetectable).
Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 15 Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) The AUC is defined as area under the plasma concentration-time curve over the dosing interval (8 hr), calculated by the lin-up/ log-down method.
Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Week 24 and Week 26 Baseline and Week 24/26 Levels of HCV RNA in plasma were measured using COBAS TaqMan HCV test v2.0. Lower limit of quantification was 25 IU/ml and limit of detection was 10 IU/ml. The assay used real time RT-PCR methodology. End of treatment (EOT) for group T2 \& PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.
Maximum Plasma Concentration (Cmax) for Telaprevir on Day 15 Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) The Cmax is defined as the maximum observed analyte concentration. The Cmax is measured in ng/ml.
Minimum Plasma Concentration (Cmin) for Telaprevir on Day 15 Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) The Cmin is defined as minimum plasma concentration between 0 hr and dosing interval. The Cmin is measured in ng/ml.
Median Time to Virological Response (HCV RNA Level < 10 IU/ml) Baseline up to EOT Virological response was defined as having HCV RNA level less than a particular threshold which is either less than 10 IU/ml (undetectable) or less than 25 IU/ml (unquantifiable).Time to virological response was defined as the number of days from the start of medication intake necessary to go for the first time below the threshold value. The EOT for group T2 \& PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.
Percentage of Participants With Viral Breakthrough Baseline, Day 12, 15 and Week 24/26 Viral breakthrough was defined as an increase in HCV RNA levels by more than 1 log10 in HCV RNA level from the lowest level reached, or a value of HCV RNA \> 100 IU/ml in participants whose HCV RNA had previously become undetectable (\< 10 IU/ml) or unquantifiable (\< 25 IU/ml) during the considered treatment phase. It was considered as confirmed when the criterion for viral breakthrough is fulfilled at two or more consecutive time points or at the last observed time point in case of trial termination. The EOT for group T2 \& PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.
Percentage of Participants Who Demonstrated Virological Relapse 24 weeks after EOT Relapse was defined as confirmed detectable HCV RNA (\>=10 IU/ml) during the follow-up period up to 24 weeks after last medication intake and after previous undetectable HCV RNA (\< 10 IU/ml) at EOT. No relapse was defined as having no confirmed detectable HCV RNA (\>=10 IU/ml) during the follow-up period and after previous undetectable HCV RNA (\< 10 IU/ml) at EOT. Missing follow-up means no HCV RNA measurements during the follow-up period and after previous undetectable HCV RNA (\< 10 IU/ml) at EOT. The EOT for group T2 \& PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.
Percentage of Participants Who Achieved Sustained Virological Response (SVR) Week 12, 24 after EOT The SVR was defined as having HCV RNA undetectable at EOT, not showing relapse up to follow-up Week 12 (SVR12) or follow-up Week 24 (SVR24), and HCV RNA undetectable at follow-up Week 12 (SVR12) or follow-up Week 24 (SVR24), respectively. The EOT for group T2 \& PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.