An Open-Label Study of Telaprevir Administered Every 12 or 8 Hours in Combination With One of Two Pegylated Interferons and Ribavirin in Treatment-Naive Genotype 1 Chronic Hepatitis C Participants

A Phase IIa Randomized, Open-Label Study of Telaprevir (VX-950) Administered Every 12 or Every 8 Hours in Combination With Either Peg-IFN alfa2a (Pegasys) and Ribavirin (Copegus) or Peg-IFN alfa2b (PegIntron) and Ribavirin (Rebetol) in Treatment-Naive Subjects With Chronic Genotype 1 Hepatitis C Infection

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00528528

Enrollment

166

Registered

2007-09-12

Start date

2007-10-31

Completion date

2009-08-31

Last updated

2014-06-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C

Keywords

Chronic Hepatitis C, Genotype 1, Telaprevir, Treatment-naïve, VX-950-C208, VX-950-TiDP24-C208

Brief summary

The purpose of this study is to explore the efficacy, safety, tolerability, pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), and pharmacokinetic-pharmacodynamic relationships of telaprevir administered in two different doses in combination with two standard therapies commercially available for chronic (lasting a long time) genotype 1 Hepatitis (inflammation of the liver) C virus (HCV) infection.

Detailed description

This is a Phase 2a, open-label (all people know the identity of the intervention), multicenter trial (conducted in more than one center) in participants with chronic genotype 1 HCV infection. The trial consists of a Screening phase of approximately 4 weeks, a treatment phase up to 48 weeks depending on participants' individual virologic response, and a follow-up phase of at least 24 weeks. All participants will receive 12 weeks of telaprevir treatment in combination with standard therapy. At Week 12, telaprevir dosing will end and participants will continue on standard therapy only. Participants will be randomly assigned to receive one of the two different dosage regimens of telaprevir (750 milligram \[mg\] every 8 hours (hr), or 1125 mg every 12 hr) in combination with standard therapy (pegylated interferon \[Peg-IFN\]-alfa-2a and ribavirin \[RBV\] or Peg-IFN-alfa-2b and RBV at the standard doses). Efficacy will be evaluated by HCV Ribonucleic Acid (RNA) values, viral response, viral breakthrough, partial response, early viral kinetics and sustained viral response. Pharmacokinetics, Pharmacokinetic-pharmacodynamic relationship will also be evaluated. Safety will be monitored throughout the study duration.

Interventions

DRUGTelaprevir

Oval tablets containing 375 mg of telaprevir for oral administration.

DRUGPeg-IFN-alfa-2a

Solution containing Peg-IFN alfa2a for subcutaneous injection in a pre-filled syringe.

DRUGPeg-IFN-alfa-2b

Powder containing Peg-IFN-alfa-2b and solvent for solution for subcutaneous injection in a pre-filled pen.

DRUGRibavirin (RBV) tablet

Tablets containing 200 mg RBV for oral administration.

DRUGRibavirin (RBV) capsule

Capsules containing 200 mg RBV for oral administration.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Chronic genotype 1 Hepatitis (inflammation of the liver) C infection * Never been treated for Hepatitis C Viral (HCV) infection * No clinically significant lab abnormalities * Amount of HCV Ribonucleic acid (RNA) in the blood more than 10,000 international units/milliliter (IU/mL) at entry * Liver biopsy or Fibroscan test performed during screening or in the past 3 years

Exclusion criteria

* Contra-indications for starting anti-HCV therapy * 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 * Any evidence of significant liver disease in addition to Hepatitis C * Infected with Human Immunodeficiency Virus (a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) or Hepatitis B * Women who are pregnant (carrying an unborn baby), planning to be pregnant or breastfeeding or the partner of a woman who is pregnant or breastfeeding

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Virologic Response at Week 12	End of treatment (EOT) (up to Week 48)	Virologic response was either defined as having undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 international units/milliliter (IU/mL) HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).

Secondary

Measure	Time frame	Description
Number of Participants With Viral Breakthrough at End of Treatment (EOT)	EOT (up to Week 48)	Viral breakthrough was defined as a confirmed increase of more than 1 log 10 in HCV RNA level from the lowest level reached or a confirmed value of HCV RNA more than 100 IU/mL in participants whose HCV RNA was previously less than 25 IU/mL.
Percentage of Participants With Partial Response	Baseline (Day 1) up to EOT (up to Week 48)	Partial response was defined as having at least 2 log drop in HCV RNA from Baseline, but not having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples).
Time to First Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level	Baseline (Day 1) up to EOT (up to Week 48)	Virologic response was either defined as having undetectable HCV RNA (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).
Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at End of Treatment (EOT)	Baseline (pre-dose), EOT (up to Week 48)	Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology.
Percentage of Participants With Sustained Viral Response 24 Weeks After End of Treatment (SVR24)	EOT (up to Week 48) and up to 24 weeks after EOT	SVR24 was defined as having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples) at EOT and no confirmed detectable HCV RNA levels between EOT and 24 weeks after the last dose of study medication.
Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at Week 12	Baseline (pre-dose), Week 12	Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology. HCV RNA samples were taken pre-dose of Peg-IFN administration.

Countries

Austria, Belgium, France, Germany, Netherlands, Spain

Participant flow

Pre-assignment details

Out of 166 participants who were randomly assigned to treatment, only 161 participants received the study treatment.

Participants by arm

Arm	Count
Telaprevir 750 mg With Peg-IFN-alfa-2a/RBV Tablet Telaprevir tablets at the dose of 750 milligram (mg) orally administered every 8 hours (hr) for 12 weeks, in combination with standard treatment composed of pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day up to 48 weeks.	40
Telaprevir 750 mg With Peg-IFN-alfa-2b/RBV Capsule Telaprevir tablets at the dose of 750 mg orally administered every 8 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kilogram/week (mcg/kg/week) and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks.	42
Telaprevir 1125 mg With Peg-IFN-alfa-2a/RBV Tablet Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2a solution for subcutaneous injection at the dose of 180 mcg/week and RBV oral tablets at the dose of 1000-1200 mg/day up to 48 weeks.	40
Telaprevir 1125 mg With Peg-IFN-alfa-2b/RBV Capsule Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kg/week and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks.	39
Total	161

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Ineligible to continue the trial	0	0	0	1
Overall Study	Lost to Follow-up	0	0	1	1
Overall Study	Ongoing participant	0	0	1	0
Overall Study	Other	0	1	0	0
Overall Study	Withdrawal by Subject	3	2	1	1

Baseline characteristics

Characteristic	Telaprevir 750 mg With Peg-IFN-alfa-2a/RBV Tablet	Telaprevir 750 mg With Peg-IFN-alfa-2b/RBV Capsule	Telaprevir 1125 mg With Peg-IFN-alfa-2a/RBV Tablet	Telaprevir 1125 mg With Peg-IFN-alfa-2b/RBV Capsule	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	40 Participants	41 Participants	40 Participants	39 Participants	160 Participants
Age, Continuous	46.5 Years	45.5 Years	40 Years	49 Years	46 Years
Region of Enrollment Austria	1 Participants	1 Participants	1 Participants	3 Participants	6 Participants
Region of Enrollment Belgium	6 Participants	5 Participants	8 Participants	4 Participants	23 Participants
Region of Enrollment France	13 Participants	17 Participants	12 Participants	13 Participants	55 Participants
Region of Enrollment Germany	13 Participants	11 Participants	11 Participants	11 Participants	46 Participants
Region of Enrollment Italy	1 Participants	3 Participants	2 Participants	3 Participants	9 Participants
Region of Enrollment Netherland	1 Participants	1 Participants	2 Participants	1 Participants	5 Participants
Region of Enrollment Spain	5 Participants	4 Participants	4 Participants	4 Participants	17 Participants
Sex: Female, Male Female	20 Participants	22 Participants	19 Participants	20 Participants	81 Participants
Sex: Female, Male Male	20 Participants	20 Participants	21 Participants	19 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	40 / 40	41 / 42	39 / 40	39 / 39
serious Total, serious adverse events	5 / 40	1 / 42	4 / 40	1 / 39

Outcome results

Primary

Percentage of Participants With Virologic Response at Week 12

Virologic response was either defined as having undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 international units/milliliter (IU/mL) HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).

Time frame: End of treatment (EOT) (up to Week 48)

Population: Full analysis set (FAS) population included all randomly assigned participants who received at least 1 dose of the study medication.

Arm	Measure	Value (NUMBER)
Telaprevir 750 mg With Peg-IFN-alfa-2a/RBV Tablet	Percentage of Participants With Virologic Response at Week 12	92.5 Percentage of participants
Telaprevir 750 mg With Peg-IFN-alfa-2b/RBV Capsule	Percentage of Participants With Virologic Response at Week 12	88.1 Percentage of participants
Telaprevir 1125 mg With Peg-IFN-alfa-2a/RBV Tablet	Percentage of Participants With Virologic Response at Week 12	92.5 Percentage of participants
Telaprevir 1125 mg With Peg-IFN-alfa-2b/RBV Capsule	Percentage of Participants With Virologic Response at Week 12	87.2 Percentage of participants

Secondary

Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at End of Treatment (EOT)

Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology.

Time frame: Baseline (pre-dose), EOT (up to Week 48)