Hepatitis C, Chronic
Conditions
Brief summary
This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered concomitantly with peg-interferon alfa-2b (Peg-IFN) and ribavirin (RBV) to treatment-naïve participants with chronic genotype 2 (GT2) or genotype 3 (GT3) hepatitis C virus (HCV) infections.
Interventions
DRUGGrazoprevir
Grazoprevir 100 mg tablets once daily for 12 weeks.
Placebo to Grazoprevir once daily for 12 weeks
DRUGPeginterferon alfa-2b (Peg-IFN)
Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks
DRUGRibavirin (RBV)
Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight ≥ 88 lbs and ≤ 275 lbs * Documented chronic Hepatitis C (CHC) GT2 or GT3 infection * No known cirrhosis * Agrees to use two acceptable methods of birth control during study and through 6 months after last dose of study drug * Chest X-ray within the last 6 months * Eye exam within the last 6 months
Exclusion criteria
* Known to be human immunodeficiency virus (HIV) positive or co-infected with active hepatitis B virus (positive for Hepatitis B surface antigen) * Prior approved or investigational treatment for hepatitis C * Evidence of hepatocellular carcinoma * Diabetic and/or high blood pressure with clinically significant eye exam findings * Pre-existing psychiatric condition * Clinical diagnosis of abuse of certain substances within specified timeframes * Known medical condition that could interfere with participation * Active or suspected cancer within the last 5 years * Female who is pregnant, breastfeeding, or expecting to conceive or donate eggs * Male who is planning to impregnate partner or donate sperm * Male with a pregnant female partner * Chronic hepatitis not caused by HCV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Complete Early Virologic Response (cEVR) in the Grazoprevir Treatment Arms | Week 12 | cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v.2.0 assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Rapid Viral Response (RVR) | Week 4 | RVR was defined as undetectable HCV RNA at Week 4. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
| Number of Participants Achieving Sustained Viral Response 12 Weeks After Completion of Therapy (SVR12) | Week 24 for Grazoprevir treatment arms, Week 36 for Placebo arm | SVR12 was defined as undetectable HCV RNA 12 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
| Time to First Achievement of Undetectable HCV Ribonucleic Acid (RNA) | Baseline to Week 12 for Grazoprevir treatment arms, Week 24 for Placebo arm | Time to first achievement of undetectable HCV RNA was determined by measuring HCV RNA at Treatment Days 1, 3, and 7; Treatment Weeks 2, 4, 8, 12, 16, 20, and 24; as well as Follow-up Weeks 4, 12, and 24. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
| Number of Participants Achieving Undetectable HCV RNA at Week 12 in the Placebo Arm | Week 12 | HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
| Number of Participants Achieving Complete Early Virologic Response (cEVR) at Week 24 in the Placebo Arm | Week 24 | cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 24 (i.e., after 12 weeks of placebo + 12 weeks of grazoprevir treatment). HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
| Number of Participants Achieving Sustained Viral Response 24 Weeks After Completion of Therapy (SVR24) | Week 36 for Grazoprevir treatment arms, Week 48 for Placebo arm | SVR24 was defined as undetectable HCV RNA 24 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. |
Participant flow
Pre-assignment details
No participants were randomized to the Grazoprevir 800 mg + Peg-IFN + RBV arm.
Participants by arm
| Arm | Count |
|---|---|
| Grazoprevir 400 mg + Peg-IFN + RBV Grazoprevir 400 mg once daily by mouth in combination with Peg-IFN and RBV for 12 weeks. | 2 |
| Placebo + Peg-IFN + RBV Placebo to grazoprevir once daily by mouth in combination with Peg-IFN and RBV for 12 weeks, followed by open-label Peg-IFN and RBV for an additional 12 weeks. | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor. | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Grazoprevir 400 mg + Peg-IFN + RBV | Placebo + Peg-IFN + RBV | Total |
|---|---|---|---|
| Age, Continuous | 40.5 years STANDARD_DEVIATION 7.8 | 51.0 years STANDARD_DEVIATION 0 | 44.0 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Number of Participants Achieving Complete Early Virologic Response (cEVR) in the Grazoprevir Treatment Arms
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v.2.0 assay.
Time frame: Week 12
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Number of Participants Achieving Complete Early Virologic Response (cEVR) at Week 24 in the Placebo Arm
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 24 (i.e., after 12 weeks of placebo + 12 weeks of grazoprevir treatment). HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Week 24
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Number of Participants Achieving Rapid Viral Response (RVR)
RVR was defined as undetectable HCV RNA at Week 4. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Week 4
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Number of Participants Achieving Sustained Viral Response 12 Weeks After Completion of Therapy (SVR12)
SVR12 was defined as undetectable HCV RNA 12 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Week 24 for Grazoprevir treatment arms, Week 36 for Placebo arm
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Number of Participants Achieving Sustained Viral Response 24 Weeks After Completion of Therapy (SVR24)
SVR24 was defined as undetectable HCV RNA 24 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Week 36 for Grazoprevir treatment arms, Week 48 for Placebo arm
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Number of Participants Achieving Undetectable HCV RNA at Week 12 in the Placebo Arm
HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Week 12
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.
Secondary
Time to First Achievement of Undetectable HCV Ribonucleic Acid (RNA)
Time to first achievement of undetectable HCV RNA was determined by measuring HCV RNA at Treatment Days 1, 3, and 7; Treatment Weeks 2, 4, 8, 12, 16, 20, and 24; as well as Follow-up Weeks 4, 12, and 24. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time frame: Baseline to Week 12 for Grazoprevir treatment arms, Week 24 for Placebo arm
Population: The Full Analysis Set (FAS) population includes all randomized participants who received at least 1 dose of study treatment. No participants completed treatment, and no analyses were conducted for this study due to early termination.