A Phase IIa Randomized, Partially Blinded Trial of Telaprevir (VX-950) in Treatment-Naive Subjects With Chronic Genotype 2 or 3 Hepatitis C Infection
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 52
- Primary Endpoint
- Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Day 15
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2
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.
Intervention: Telaprevir (Drug)
TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2
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.
Intervention: Telaprevir (Drug)
TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 2
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 2
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.
Intervention: Placebo (Drug)
TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 3
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.
Intervention: Telaprevir (Drug)
TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 3
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 3
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.
Intervention: Telaprevir (Drug)
TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 3
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 3
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.
Intervention: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment) (Drug)
Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 3
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Day 15
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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))
- 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)
- Maximum Plasma Concentration (Cmax) for Telaprevir on Day 15(Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr))
- Minimum Plasma Concentration (Cmin) for Telaprevir on Day 15(Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr))
- 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))
- Median Time to Virological Response (HCV RNA Level < 10 IU/ml)(Baseline up to EOT)
- Percentage of Participants With Viral Breakthrough(Baseline, Day 12, 15 and Week 24/26)
- Percentage of Participants Who Demonstrated Virological Relapse(24 weeks after EOT)
- Percentage of Participants Who Achieved Sustained Virological Response (SVR)(Week 12, 24 after EOT)