Hepatitis C Virus (HCV)
Conditions
Keywords
Chronic Hepatitis C Infection
Brief summary
This study seeks to assess the safety and efficacy of treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in non-cirrhotic, genotype 1a (GT1a) hepatitis C virus infected participants who are treatment-naïve or treatment-experienced with Interferon (IFN) or Pegylated Interferon (pegIFN) with or without Ribavirin (RBV).
Interventions
Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet
DRUGribavirin
Tablet
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV) infection * Non-cirrhotic subjects * Screening laboratory results showing HCV Genotype 1a (HCV GT1a) infection * HCV treatment-naïve or if treated previously, only with interferon (IFN) or pegylated interferon (pegINF) with or without ribavirin (RBV)
Exclusion criteria
* Pregnant or breastfeeding women * Positive for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) * HCV genotype of any subtype other than GT1a or unable to subtype * Prior or current use of any investigational or commercially available anti-HCV agents other than IFN, pegIFN or RBV. Subjects with previous participation in trials of investigational direct-acting antiviral agents (DAAs) may be enrolled if they can produce documentation that they received only placebo. * Current enrollment in another interventional clinical study or receipt of any investigational product within 6 weeks prior to study drug administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after the last actual dose of study drug | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in participants in the treatment arm 3-DAA + RBV 600 mg) for 12 weeks compared with the historical control rate for subjects treated with 3-DAA + weight-based RBV for 12 weeks. |
| Percentage of Participants With Hemoglobin < 10 g/dL During Treatment | up to 12 weeks | The percentage of participants with hemoglobin \<10 g/dL during treatment is provided. |
| Mean Change in Hemoglobin Values From Baseline to End of Treatment | Baseline (Day 1) to Weeks 2, 4, 8, and 12, and the Final Treatment Visit (up to 12 weeks) | The mean change in hemoglobin (g/L) from baseline to each study visit and to the final treatment visit (up to 12 weeks) is provided. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | Up to 12 weeks | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment through 12 weeks after the last dose of study drug | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug, excluding reinfection, among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3-DAA + RBV 600 mg 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 mg once daily\] and dasabuvir \[250 mg twice daily\]) plus RBV (ribavirin \[600 mg once daily\]) for 12 weeks. | 105 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | 3-DAA + RBV 600 mg |
|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 13.03 |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / 105 |
| serious Total, serious adverse events | 3 / 105 |
Outcome results
Primary
Mean Change in Hemoglobin Values From Baseline to End of Treatment
The mean change in hemoglobin (g/L) from baseline to each study visit and to the final treatment visit (up to 12 weeks) is provided.
Time frame: Baseline (Day 1) to Weeks 2, 4, 8, and 12, and the Final Treatment Visit (up to 12 weeks)
Population: All participants who received at least 1 dose of study drug (ITT population) with a hemoglobin value at baseline and at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3-DAA + RBV 600 mg | Mean Change in Hemoglobin Values From Baseline to End of Treatment | Week 2 | -6.4 g/L | Standard Deviation 8.17 |
| 3-DAA + RBV 600 mg | Mean Change in Hemoglobin Values From Baseline to End of Treatment | Week 4 | -8.9 g/L | Standard Deviation 9.37 |
| 3-DAA + RBV 600 mg | Mean Change in Hemoglobin Values From Baseline to End of Treatment | Week 8 | -11.2 g/L | Standard Deviation 9.85 |
| 3-DAA + RBV 600 mg | Mean Change in Hemoglobin Values From Baseline to End of Treatment | Week 12 | -12.4 g/L | Standard Deviation 10.06 |
| 3-DAA + RBV 600 mg | Mean Change in Hemoglobin Values From Baseline to End of Treatment | Final Treatment Visit | -12.1 g/L | Standard Deviation 9.9 |
Primary
Percentage of Participants With Hemoglobin < 10 g/dL During Treatment
The percentage of participants with hemoglobin \<10 g/dL during treatment is provided.
Time frame: up to 12 weeks
Population: All participants who received at least 1 dose of study drug (ITT population) with at least one post-baseline hemoglobin value through the final treatment value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA + RBV 600 mg | Percentage of Participants With Hemoglobin < 10 g/dL During Treatment | 0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in participants in the treatment arm 3-DAA + RBV 600 mg) for 12 weeks compared with the historical control rate for subjects treated with 3-DAA + weight-based RBV for 12 weeks.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent-to-treat population: all participants who received at least 1 dose of study drug; participants with missing data after flanking imputation were counted as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA + RBV 600 mg | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 89.5 percentage of participants |
95% CI: [83.7, 95.4]
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of treatment.
Time frame: Up to 12 weeks
Population: All participants who received at least 1 dose of study drug (ITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA + RBV 600 mg | Percentage of Participants With On-treatment Virologic Failure | 1.0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug, excluding reinfection, among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment.
Time frame: From the end of treatment through 12 weeks after the last dose of study drug
Population: All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA + RBV 600 mg | Percentage of Participants With Post-treatment Relapse | 4.1 percentage of participants |