Hepatitis C
Conditions
Keywords
HCV, Hepatitis C Genotype 1
Brief summary
Evaluate safety, tolerability, and antiviral response of ACH-0141625 compared to standard of care in hepatitis C virus (HCV)-positive participants.
Interventions
DRUGACH-0141625 (Sovaprevir)
200 mg oral capsule once daily
DRUGPlacebo
Powder in capsule once daily
180 micrograms (ug) once a week by subcutaneous injection
DRUGRibavirin
400 mg or 600 mg (morning \[AM\]) and 600 mg (evening \[PM\]) capsules taken orally twice daily
Sponsors
Achillion, a wholly owned subsidiary of Alexion
Alexion Pharmaceuticals, Inc.
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
* Males and females, aged 18 years and older * Chronic hepatitis C genotype 1 (as specified in the protocol) * Treatment naive * Females who are post-menopausal and amenorrheic must have a follicle-stimulating hormone (FSH) at screening. Females of childbearing potential must have a negative pregnancy test at screening and baseline. Females must use a non-hormonal method of contraception and must agree not to get pregnant during the study and for 6 months following the discontinuation of standard of care (SOC). * Fertile males must agree to use a condom and his female partner must agree to use 1 or more methods of contraception. Males must not donate sperm during the study and 3 months following the last exposure to RBV.
Exclusion criteria
* Body mass index (BMI) \>36 kilograms (kg)/square meter (m\^2) * Pregnant or nursing females or females of childbearing potential not willing to comply with contraceptive measures per protocol. Men whose female partners are pregnant or contemplating pregnancy. - Coinfection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) * Other significant diseases including liver disease * History of drug or alcohol dependence or addiction within the past 6 months * History of participation in a clinical trial with a protease inhibitor or previous treatment with a protease inhibitor, where at least 1 dose of the protease inhibitor was consumed. * Use of herbal or homeopathic products, illicit drugs, cytochrome P450 (CYP) 3A4/5 substrates, inducers or inhibitors, hormonal methods of contraception, corticosteroids, immunosuppressive, or cytotoxic agents within 28 days of the first dose of study drug. * Have a clinically significant laboratory abnormality at screening (as specified in the protocol). * Segment 1: Participants with any history of decompensated liver disease defined as cirrhotic participants with a Child-Pugh score of \> or = to 7. Segment 2: Participants who have had a liver biopsy that shows bridging fibrosis or cirrhosis. * Nonalcoholic steatohepatitis if ballooning degeneration or Mallory bodies are present on liver biopsy. * Participants who prematurely discontinued, interrupted, or dose reduced prior Peg-IFN and RBV therapy due to noncompliance or safety issues. * Encephalopathy or altered mental status of any etiology. * History of moderate, severe, or uncontrolled psychiatric disease (as specified in the protocol). * History of malignancy of any organ system treated or untreated within the past 5 years. * Use of colony stimulating factor agents within 90 days prior to baseline. * History of seizure disorder. * History of known coagulopathy including hemophilia. * Clinically of significant findings on fundoscopic or retinal examination at screening * History of immunologically mediate disease. * History of clinical evidence of chronic cardiac disease (as specified in the protocol) * Received concomitant systemic antibiotic, antifungals, or antivirals for the treatment of active infection within 14 days prior to the first dose of the study drug (as specified in the protocol)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Segment 1: Safety | 4 weeks | Segment 1: Percentage of participants with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening Division of AIDS (Acquired Immunodeficiency Syndrome) (DAIDs) graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Segment 1: Rapid Viral Response At Week 4 (RVR4) | 4 weeks | The primary efficacy endpoint for Segment 1 of the study was the percentage of participants in each treatment group achieving RVR4 (hepatitis C virus \[HCV\] ribonucleic acid (RNA) less than or equal to the limit of quantitation \[LOQ\] at the Week 4 visit). |
| Segment 2: Safety | 12 weeks | Segment 2: Percentage of participants with the following: adverse events, abnormal laboratory safety tests and dose reductions, interruptions and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Segment 2: Complete Early Virologic Response (cEVR) | Week 12 | The primary efficacy endpoint for Segment 2 of the study was the percentage of participants achieving cEVR, defined as undetectable HCV RNA at Week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 6 months post-dosing | The percentage of virology population participants who achieved SVR, defined as HCV RNA less than the LOQ, 6 months post-dosing. |
| Segment 1: cEVR | 12 weeks | For Segment 1, the percentage of participants in the virology population who achieved cEVR, defined as undetectable HCV RNA at Week 12. |
| Segment 1 And Segment 2: HCV RNA Change From Baseline | Week 4 | The mean change from baseline in log10 HCV RNA level by visit for the virology population |
| Segment 2: RVR4 | 4 weeks | For Segment 2, the percentage of participants in the virology population who achieved RVR4, defined as HCV RNA less than or equal to the LOQ at the Week 4 visit. |
| Segment 1 And Segment 2: End Of Treatment Response | Week 48 (Segment 1); Week 24 (Segment 2) | The percentage of virology population participants who were reported as undetectable HCV RNA at the completion of treatment. |
| Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 3 months post-dosing | The percentage of virology population participants who achieved sustained virologic response (SVR), defined as HCV RNA less than the LOQ, at 12 weeks (3 months) post-dosing. |
Countries
Belgium, United States
Participant flow
Recruitment details
Participants were recruited from 15 sites in the United States and 3 sites in Belgium between 30 September 2010 and 03 January 2012.
Pre-assignment details
Participants were screened within 4 weeks (Day -28 to Day -1) before administration of the study drug. Participants who meet all eligibility criteria were instructed to arrive at the study center on Baseline day for randomization to treatment assignment.
Participants by arm
| Arm | Count |
|---|---|
| Segment 1: 200 mg ACH-0141625 200 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a and RBV for 48 weeks
ACH-0141625: 200 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 16 |
| Segment 1: 400 mg ACH-0141625 400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
ACH-0141625: 400 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 16 |
| Segment 1: 800 mg ACH-0141625 800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
ACH-0141625: 800 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 17 |
| Segment 1: Placebo Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Placebo: Powder in capsule once daily for 28 days
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 15 |
| Segment 2: 200 mg ACH-0141625 200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 48 weeks
ACH-0141625: 200 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 19 |
| Segment 2: 400 mg ACH-0141625 400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 48 weeks
ACH-0141625: 400 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 20 |
| Segment 2: 800 mg ACH-0141625 800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 48 weeks
ACH-0141625: 800 mg oral capsule once daily for 28 days or for 12 weeks
Peg-IFN alpha-2a: 180 ug once a week by subcutaneous injection for 48 weeks
RBV: 400 mg or 600 mg (AM) and 600 mg (PM) capsules taken orally twice daily for 48 weeks | 19 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 | 0 | 1 | 3 | 0 |
| Overall Study | compliance | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 2 | 5 | 6 | 1 | 3 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 | 0 | 2 | 1 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Severe coronary atherosclerosis (death) | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 5 | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Segment 1: 400 mg ACH-0141625 | Segment 1: 800 mg ACH-0141625 | Segment 1: Placebo | Segment 2: 200 mg ACH-0141625 | Segment 2: 400 mg ACH-0141625 | Segment 2: 800 mg ACH-0141625 | Segment 1: 200 mg ACH-0141625 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 16 Participants | 15 Participants | 19 Participants | 19 Participants | 19 Participants | 15 Participants | 119 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 13 | 47 years STANDARD_DEVIATION 9 | 45 years STANDARD_DEVIATION 11 | 48 years STANDARD_DEVIATION 12 | 42 years STANDARD_DEVIATION 12 | 51 years STANDARD_DEVIATION 7 | 48 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 4 Participants | 7 Participants | 5 Participants | 9 Participants | 3 Participants | 38 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 11 Participants | 12 Participants | 15 Participants | 10 Participants | 13 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 15 / 16 | 17 / 17 | 18 / 19 | 17 / 20 | 19 / 19 | 14 / 15 |
| serious Total, serious adverse events | 2 / 16 | 1 / 16 | 5 / 17 | 0 / 19 | 2 / 20 | 0 / 19 | 0 / 15 |
Outcome results
Primary
Segment 1: Rapid Viral Response At Week 4 (RVR4)
The primary efficacy endpoint for Segment 1 of the study was the percentage of participants in each treatment group achieving RVR4 (hepatitis C virus \[HCV\] ribonucleic acid (RNA) less than or equal to the limit of quantitation \[LOQ\] at the Week 4 visit).
Time frame: 4 weeks
Population: Efficacy analysis was performed on the virology population (a subset of the ITT population) and included all participants who had a baseline HCV RNA result and at least 1 post-baseline HCV RNA result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Segment 1: Placebo | Segment 1: Rapid Viral Response At Week 4 (RVR4) | No Rapid Virologic Response (%) | 80.0 percentage of participants |
| Segment 1: Placebo | Segment 1: Rapid Viral Response At Week 4 (RVR4) | Rapid Virologic Response (%) | 20.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | No Rapid Virologic Response (%) | 25.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | Rapid Virologic Response (%) | 75.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | Rapid Virologic Response (%) | 75.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | No Rapid Virologic Response (%) | 25.0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | Rapid Virologic Response (%) | 76.5 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Rapid Viral Response At Week 4 (RVR4) | No Rapid Virologic Response (%) | 23.5 percentage of participants |
Comparison: The null hypothesis is no difference between proportions of participants in each treatment group achieving RVR4 at Week 4 of the study, while the alternative hypothesis is that the proportion of participants achieving RVR4 at Week 4 increases with increasing doses of ACH-0141625.p-value: 0.003exact Cochran-Armitage test
Comparison: To control for multiplicity, the proportion in each treatment group achieving RVR4 is analyzed using a Cochran-Armitage test for trend among the ordered groups: placebo (considered zero dose), 200 mg ACH-0141625, 400 mg ACH-0141625, and 800 mg ACH-0141625. Only if overall test for trend is significant are pairwise comparisons evaluated using p-values for the difference in proportions (placebo - active).p-value: 0.004Fisher Exact
Comparison: To control for multiplicity, the proportion in each treatment group achieving RVR4 is analyzed using a Cochran-Armitage test for trend among the ordered groups: placebo (considered zero dose), 200 mg ACH-0141625, 400 mg ACH-0141625, and 800 mg ACH-0141625. Only if overall test for trend is significant are pairwise comparisons evaluated using p-values for the difference in proportions (placebo - active).p-value: 0.004Fisher Exact
Comparison: To control for multiplicity, the proportion in each treatment group achieving RVR4 is analyzed using a Cochran-Armitage test for trend among the ordered groups: placebo (considered zero dose), 200 mg ACH-0141625, 400 mg ACH-0141625, and 800 mg ACH-0141625. Only if overall test for trend is significant are pairwise comparisons evaluated using p-values for the difference in proportions (placebo - active).p-value: 0.004Fisher Exact
Primary
Segment 1: Safety
Segment 1: Percentage of participants with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening Division of AIDS (Acquired Immunodeficiency Syndrome) (DAIDs) graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: 4 weeks
Population: The safety population, which was defined as all participants randomized and treated with at least one dose of ACH-0141625 or Placebo. Participants were analyzed according to the randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Segment 1: Placebo | Segment 1: Safety | Adverse Events (%) | 93.3 percentage of participants |
| Segment 1: Placebo | Segment 1: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: Placebo | Segment 1: Safety | Dose Discontinuations (%) | 0 percentage of participants |
| Segment 1: Placebo | Segment 1: Safety | Abnormal Laboratories (%) | 100.0 percentage of participants |
| Segment 1: Placebo | Segment 1: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Safety | Abnormal Laboratories (%) | 100.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Safety | Adverse Events (%) | 100.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: Safety | Dose Discontinuations (%) | 6.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Safety | Abnormal Laboratories (%) | 100.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Safety | Adverse Events (%) | 93.8 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: Safety | Dose Discontinuations (%) | 0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Safety | Adverse Events (%) | 100.0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Safety | Abnormal Laboratories (%) | 94.0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: Safety | Dose Discontinuations (%) | 6.0 percentage of participants |
Primary
Segment 2: Complete Early Virologic Response (cEVR)
The primary efficacy endpoint for Segment 2 of the study was the percentage of participants achieving cEVR, defined as undetectable HCV RNA at Week 12.
Time frame: Week 12
Population: Per protocol virology population (a subset of the virology population) and included all randomized participants who completed 12 weeks of ACH-0141625 dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 2: Complete Early Virologic Response (cEVR) | 100.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Complete Early Virologic Response (cEVR) | 94.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Complete Early Virologic Response (cEVR) | 100.00 percentage of participants |
Comparison: The null hypothesis is no difference between proportions of participants in each treatment group achieving cEVR at Week 12 of the study, while the alternative hypothesis is that the proportion of participants achieving cEVR at Week 12 increases with increasing doses of ACH-0141625.p-value: 0.34Exact Cochran-Armitage test
Primary
Segment 2: Safety
Segment 2: Percentage of participants with the following: adverse events, abnormal laboratory safety tests and dose reductions, interruptions and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: 12 weeks
Population: The safety population, which was defined as all participants randomized and treated with at least 1 dose of ACH-0141625. Participants were analyzed according to the randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Segment 1: Placebo | Segment 2: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: Placebo | Segment 2: Safety | Abnormal Laboratories (%) | 100.0 percentage of participants |
| Segment 1: Placebo | Segment 2: Safety | Adverse Events (%) | 94.7 percentage of participants |
| Segment 1: Placebo | Segment 2: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: Placebo | Segment 2: Safety | Dose Discontinuations (%) | 6.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Safety | Abnormal Laboratories (%) | 95.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Safety | Adverse Events (%) | 85.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: Safety | Dose Discontinuations (%) | 20.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Safety | Dose Discontinuations (%) | 0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Safety | Dose Interruptions (%) | 0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Safety | Dose Reductions (%) | 0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Safety | Abnormal Laboratories (%) | 100.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: Safety | Adverse Events (%) | 100.0 percentage of participants |
Secondary
Segment 1 And Segment 2: End Of Treatment Response
The percentage of virology population participants who were reported as undetectable HCV RNA at the completion of treatment.
Time frame: Week 48 (Segment 1); Week 24 (Segment 2)
Population: Segment 2 analyzed the per protocol population (PPP), which includes all randomized participants who completed 12 weeks of ACH-0141625 dosing and an additional 12 weeks of Peg/RBV dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 1 And Segment 2: End Of Treatment Response | 75.0 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 75.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 64.7 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 53.3 percentage of participants |
| Segment 2: 200 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 100.0 percentage of participants |
| Segment 2: 400 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 92.3 percentage of participants |
| Segment 2: 800 mg ACH-0141625 | Segment 1 And Segment 2: End Of Treatment Response | 100.0 percentage of participants |
Secondary
Segment 1 And Segment 2: HCV RNA Change From Baseline
Change from baseline in log10 HCV RNA level by visit.
Time frame: Week 12
Population: Efficacy analysis was performed on the virology population, a subset of the ITT population, and included all participants who had a baseline HCV RNA result and at least 1 post-baseline HCV RNA result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Segment 1: Placebo | Segment 1 And Segment 2: HCV RNA Change From Baseline | -5.13 log10 HCV RNA level | Standard Deviation 0.518 |
| Segment 1: 200 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.51 log10 HCV RNA level | Standard Deviation 1.467 |
| Segment 1: 400 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.67 log10 HCV RNA level | Standard Deviation 1.555 |
| Segment 1: 800 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -3.48 log10 HCV RNA level | Standard Deviation 1.753 |
| Segment 2: 200 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.90 log10 HCV RNA level | Standard Deviation 1.104 |
| Segment 2: 400 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -5.08 log10 HCV RNA level | Standard Deviation 0.77 |
| Segment 2: 800 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.58 log10 HCV RNA level | Standard Deviation 0.946 |
Secondary
Segment 1 And Segment 2: HCV RNA Change From Baseline
The mean change from baseline in log10 HCV RNA level by visit for the virology population
Time frame: Week 4
Population: Efficacy analysis was performed on the virology population, which was a subset of the ITT population and included all participants who had a baseline HCV RNA result and at least 1 post-baseline HCV RNA result.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Segment 1: Placebo | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.94 log10 HCV RNA Level | Standard Deviation 0.993 |
| Segment 1: 200 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.60 log10 HCV RNA Level | Standard Deviation 1.462 |
| Segment 1: 400 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.94 log10 HCV RNA Level | Standard Deviation 1.098 |
| Segment 1: 800 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -2.22 log10 HCV RNA Level | Standard Deviation 1.447 |
| Segment 2: 200 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.74 log10 HCV RNA Level | Standard Deviation 1.072 |
| Segment 2: 400 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -5.04 log10 HCV RNA Level | Standard Deviation 0.738 |
| Segment 2: 800 mg ACH-0141625 | Segment 1 And Segment 2: HCV RNA Change From Baseline | -4.51 log10 HCV RNA Level | Standard Deviation 0.941 |
Secondary
Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12)
The percentage of virology population participants who achieved sustained virologic response (SVR), defined as HCV RNA less than the LOQ, at 12 weeks (3 months) post-dosing.
Time frame: 3 months post-dosing
Population: Segment 2 analyzed the PPP (all randomized participants completing 12 weeks of ACH-0141625 + an extra 12 weeks of Peg/RBV) who returned for SVR12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 56.3 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 56.3 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 35.3 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 40.0 percentage of participants |
| Segment 2: 200 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 80.0 percentage of participants |
| Segment 2: 400 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 76.9 percentage of participants |
| Segment 2: 800 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | 84.5 percentage of participants |
Secondary
Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24)
The percentage of virology population participants who achieved SVR, defined as HCV RNA less than the LOQ, 6 months post-dosing.
Time frame: 6 months post-dosing
Population: Segment 2 analyzed the PPP (all randomized participants completing 12 weeks of ACH-0141625 plus an extra 12 weeks of Peg/RBV) who returned for SVR24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 62.5 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 56.3 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 35.3 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 40.0 percentage of participants |
| Segment 2: 200 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 70.0 percentage of participants |
| Segment 2: 400 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 76.9 percentage of participants |
| Segment 2: 800 mg ACH-0141625 | Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | 83.3 percentage of participants |
Secondary
Segment 1: cEVR
For Segment 1, the percentage of participants in the virology population who achieved cEVR, defined as undetectable HCV RNA at Week 12.
Time frame: 12 weeks
Population: Analysis for Segment 1 was performed on the virology population (the same as the ITT population) and included all participants who had a baseline HCV RNA result and at least 1 post-baseline HCV RNA result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 1: cEVR | 62.5 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 1: cEVR | 75.0 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 1: cEVR | 70.6 percentage of participants |
| Segment 1: 800 mg ACH-0141625 | Segment 1: cEVR | 33.3 percentage of participants |
Secondary
Segment 2: RVR4
For Segment 2, the percentage of participants in the virology population who achieved RVR4, defined as HCV RNA less than or equal to the LOQ at the Week 4 visit.
Time frame: 4 weeks
Population: Per protocol virology population (a subset of the virology population) and included all randomized participants who completed 4 weeks of ACH-0141625 dosing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Segment 1: Placebo | Segment 2: RVR4 | 78.9 percentage of participants |
| Segment 1: 200 mg ACH-0141625 | Segment 2: RVR4 | 88.8 percentage of participants |
| Segment 1: 400 mg ACH-0141625 | Segment 2: RVR4 | 89.5 percentage of participants |