Chronic Hepatitis C(CHC)
Conditions
Keywords
Feron
Brief summary
This study will evaluate the efficacy and safety of MP-424 with IFN beta and RBV in patients with genotype 1/2 hepatitis C, who are treatment-naïve or have received its treatment before.
Interventions
DRUGMP-424
MP-424: 750mg every 8 hours (q8h) for 12 weeks
DRUGRBV(24 weeks)
RBV: 600 - 1000mg/day based on body weight for 24 weeks
DRUGIFN beta(24 weeks)
IFN beta: 600 MIU/day,6 days/week for initial 4 weeks following to 3 days/week for 24 weeks
DRUGRBV(48 weeks)
RBV: 600 - 1000mg/day based on body weight for 48 weeks
DRUGIFN beta(48 weeks)
IFN beta: 600 MIU/day,6 days/week for initial 4 weeks following to 3 days/week for 48 weeks
Sponsors
Toray Industries, Inc
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Genotype 1 or 2, chronic hepatitis C, with depression(including the past) * Treatment-naïve(Genotype 1 only) or patient who have ever had previous IFN based treatment * Able and willing to follow contraception requirements
Exclusion criteria
* Cirrhosis of the liver or hepatic failure * Hepatitis B surface antigen-positive or HIV antibodies-positive * History of, or concurrent hepatocellular carcinoma * History of, or concurrent serious depression, schizophrenia, or suicide attempt in the past * Pregnant, lactating, or suspected pregnant patients, or male patients whose female partner is pregnant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response) | 72 weeks(RBV+IFN beta), 48 weeks(MP-424+RBV+IFN beta) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response) | 4 weeks | — |
| Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response) | 48 weeks(RBV+IFN beta), 24 weeks(MP-424+RBV+IFN beta) | — |
| Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration | 60 weeks(RBV+IFN beta), 36 weeks(MP-424+RBV+IFN beta) | — |
| Transition of Serum HCV RNA Levels | Baseline，Day2，Day3，1Week，2Weeks，3Weeks，4Weeks，12Weeks，End of treatment，Follow-up 12weeks，Follow-up 24weeks | — |
| Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | From baseline to 24 weeks after completion of drug administration | To examine the emergence of resistance-associated variants after MP-424 administration. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MP-424+RBV+IFN Beta, Genotype1 Drug: MP-424 MP-424: 750mg every 8 hours (q8h) for 12 weeks Drug: RBV RBV: 600 - 1000 mg/day based on body weight for 24 weeks Drug: IFN beta IFN beta: 600 MIU/day,6 days/week for initial 4 weeks following to 3days /week for 24 weeks | 30 |
| RBV+IFN Beta, Genotype1 Drug: RBV RBV: 600 - 1000 mg/day based on body weight for 48 weeks Drug: IFN beta IFN beta: 600 MIU/day,6 days/week for initial 4 weeks following to 3days /week for 48 weeks | 30 |
| MP-424+RBV+IFN Beta, Genotype2 Drug: MP-424 MP-424: 750mg every 8 hours (q8h) for 12 weeks Drug: RBV RBV: 600 - 1000 mg/day based on body weight for 24 weeks Drug: IFN beta IFN beta: 600 MIU/day,6 days/week for initial 4 weeks following to 3days /week for 24 weeks | 14 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 4 | 0 |
Baseline characteristics
| Characteristic | MP-424+RBV+IFN Beta, Genotype1 | RBV+IFN Beta, Genotype1 | MP-424+RBV+IFN Beta, Genotype2 | Total |
|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 6.4 | 57.6 years STANDARD_DEVIATION 10.5 | 55.4 years STANDARD_DEVIATION 7.7 | 58.4 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 22 Participants | 21 Participants | 9 Participants | 52 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 5 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 30 | 30 / 30 | 14 / 14 |
| serious Total, serious adverse events | 4 / 30 | 3 / 30 | 5 / 14 |
Outcome results
Primary
Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response)
Time frame: 72 weeks(RBV+IFN beta), 48 weeks(MP-424+RBV+IFN beta)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response) | 63.3 percentage of subjects achieving SVR |
| RBV+IFN Beta, Genotype1 | Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response) | 20.0 percentage of subjects achieving SVR |
| MP-424+RBV+IFN Beta, Genotype2 | Undetectable HCV (Hepatitis C Virus) RNA (Ribonucleic Acid) at 24 Weeks After Completion of Drug Administration (SVR, Sustained Viral Response) | 71.4 percentage of subjects achieving SVR |
Secondary
Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV.
To examine the emergence of resistance-associated variants after MP-424 administration.
Time frame: From baseline to 24 weeks after completion of drug administration
Population: Overall number of participants analyzed indicates the number of participants who did not achieve SVR and detected HCV RNA as positive at the last visit in each group, MP-424+RBV+IFN Beta, Genotype1 and MP-424+RBV+IFN Beta, Genotype2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54A | 1 participants |
| MP-424+RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54A，R155W | 0 participants |
| MP-424+RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54S，A156T，V36A | 1 participants |
| MP-424+RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | Not detected | 5 participants |
| MP-424+RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | V36M | 1 participants |
| RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | Not detected | 1 participants |
| RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | V36M | 0 participants |
| RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54A | 0 participants |
| RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54S，A156T，V36A | 0 participants |
| RBV+IFN Beta, Genotype1 | Number of Participants With the Emergence of Resistance-associated Variants After MP-424 Administration at the Non-structural 3 Protease Region of HCV. | T54A，R155W | 1 participants |
Secondary
Transition of Serum HCV RNA Levels
Time frame: Baseline，Day2，Day3，1Week，2Weeks，3Weeks，4Weeks，12Weeks，End of treatment，Follow-up 12weeks，Follow-up 24weeks
Population: Participants were excluded from analysis because of dropouts or missing data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 12Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 2Weeks | 1.30 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Follow-up 12weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 4Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 3Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Baseline | 6.73 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Day3 | 3.35 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Day2 | 4.15 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | End of treatment | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 1Week | 2.40 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Follow-up 24weeks | 0.50 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 3Weeks | 3.70 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Baseline | 6.83 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Day2 | 5.65 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Day3 | 4.85 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 1Week | 5.30 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 2Weeks | 4.60 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 4Weeks | 3.20 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | 12Weeks | 2.75 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | End of treatment | 3.20 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Follow-up 12weeks | 6.20 log IU/mL |
| RBV+IFN Beta, Genotype1 | Transition of Serum HCV RNA Levels | Follow-up 24weeks | 6.20 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | Follow-up 12weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | 12Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | Day3 | 2.80 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | Baseline | 6.05 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | End of treatment | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | Day2 | 3.80 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | 3Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | 2Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | Follow-up 24weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | 4Weeks | 0.50 log IU/mL |
| MP-424+RBV+IFN Beta, Genotype2 | Transition of Serum HCV RNA Levels | 1Week | 1.25 log IU/mL |
Secondary
Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration
Time frame: 60 weeks(RBV+IFN beta), 36 weeks(MP-424+RBV+IFN beta)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration | 66.7 percentage of subjects achieving SVR12 |
| RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration | 20.0 percentage of subjects achieving SVR12 |
| MP-424+RBV+IFN Beta, Genotype2 | Undetectable HCV RNA at 12 Weeks After Completion of Drug Administration | 71.4 percentage of subjects achieving SVR12 |
Secondary
Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response)
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response) | 70.0 percentage of subjects achieving RVR |
| RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response) | 6.7 percentage of subjects achieving RVR |
| MP-424+RBV+IFN Beta, Genotype2 | Undetectable HCV RNA at 4 Weeks After Beginning of Drug Administration (RVR, Rapid Viral Response) | 92.9 percentage of subjects achieving RVR |
Secondary
Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response)
Time frame: 48 weeks(RBV+IFN beta), 24 weeks(MP-424+RBV+IFN beta)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MP-424+RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response) | 76.7 percentage of subjects achieving ETR |
| RBV+IFN Beta, Genotype1 | Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response) | 30.0 percentage of subjects achieving ETR |
| MP-424+RBV+IFN Beta, Genotype2 | Undetectable HCV RNA at Completion of Drug Administration (ETR, End-of-treatment Response) | 85.7 percentage of subjects achieving ETR |