Hepatitis C Infection, Hepatitis C Virus
Conditions
Keywords
Hepatitis C Virus, Interferon-Free, Ribavirin-Free, Hepatitis C, Hepatitis C Genotype 1b
Brief summary
This study will evaluate the safety and efficacy of ombitasvir/paritaprevir/ ritonavir and dasabuvir administered for 8 weeks in treatment-naïve participants with genotype 1b (GT1b) hepatitis C virus (HCV).
Interventions
Tablet
DRUGdasabuvir
Tablet
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Chronic HCV infection at Screening. 2. Screening laboratory result indicating HCV genotype 1b infection. 3. Treatment-naïve and non-cirrhotic.
Exclusion criteria
1. HCV genotype or subtype other than GT1b. 2. Positive test result for Hepatitis B surface antigen (HbsAg) or confirmed positive anti-HIV antibody (HIV Ab) test. 3. Any current or past clinical evidence of cirrhosis. 4. Screening laboratory analyses that shows abnormal results. 5. Clinically significant abnormalities or co-morbidities, other than HCV infection that make the participant an unsuitable candidate for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after the last actual dose of study drug | SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantification (LLOQ) 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-Treatment Virologic Failure During Treatment Period | Up to 8 weeks while on treatment | On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements \> 1 log\^10 IU/mL above nadir) at any time point during treatment) or failure to suppress during treatment (all on-treatment values of HCV RNA ≥ LLOQ) with at least 6 weeks (defined as study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Participants With Post-Treatment Relapse12 | Up to 12 weeks after last dose of study drug | Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of active study drug (up to and including the SVR12 window) excluding reinfection among participants with HCV RNA \< LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for participants who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Female Participants Responding With SVR12 | 12 weeks after the last actual dose of study drug | SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12 | Baseline and 12 weeks after the last actual dose of study drug | SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve SVR12: mITT-GT Population | 12 weeks after the last actual dose of study drug | SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Participants With On-Treatment Virologic Failure During Treatment Period: mITT-GT Population | Up to 8 weeks while on treatment | On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements \> 1 log\^10 IU/mL above nadir) at any time point during treatment) or failure to suppress during treatment (all on-treatment values of HCV RNA ≥ LLOQ) with at least 6 weeks (defined as study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the Wilson score method. |
| Percentage of Participants With Post-Treatment Relapse12: mITT-GT Population | Up to 12 weeks after last dose of study drug | Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of active study drug (up to and including the SVR12 window) excluding reinfection among participants with HCV RNA \< LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for participants who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Female Participants Responding With SVR12: mITT-GT Population | 12 weeks after the last actual dose of study drug | SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
| Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12: mITT-GT Population | Baseline and 12 weeks after the last actual dose of study drug | SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) administered for 8 weeks | 166 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 13.42 |
| Sex: Female, Male Female | 94 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 70 / 166 |
| serious Total, serious adverse events | 2 / 166 |
Outcome results
Primary
Percentage of Participants Who Achieve Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 is defined as hepatitis C virus (HCV) ribonucleic acid (RNA) \< lower limit of quantification (LLOQ) 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent to Treat (ITT) population: all enrolled participants who received at least 1 dose of study drug. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants Who Achieve Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 97.6 percentage of participants |
Secondary
Percentage of Female Participants Responding With SVR12
SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: 12 weeks after the last actual dose of study drug
Population: ITT population: all enrolled female participants who received at least 1 dose of study drug. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Female Participants Responding With SVR12 | 97.9 percentage of participants |
Secondary
Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12
SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: Baseline and 12 weeks after the last actual dose of study drug
Population: ITT population: all enrolled participants who received at least 1 dose of study drug and with baseline HCV RNA \< 6,000,000 IU/mL. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12 | 98.1 percentage of participants |
Secondary
Percentage of Participants With On-Treatment Virologic Failure During Treatment Period
On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements \> 1 log\^10 IU/mL above nadir) at any time point during treatment) or failure to suppress during treatment (all on-treatment values of HCV RNA ≥ LLOQ) with at least 6 weeks (defined as study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: Up to 8 weeks while on treatment
Population: ITT population: all enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With On-Treatment Virologic Failure During Treatment Period | 0.6 percentage of participants |
Secondary
Percentage of Participants With Post-Treatment Relapse12
Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of active study drug (up to and including the SVR12 window) excluding reinfection among participants with HCV RNA \< LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for participants who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: Up to 12 weeks after last dose of study drug
Population: ITT population: all enrolled participants who received at least 1 dose of study drug. Participants who did not complete treatment or had no post treatment data available or had HCV RNA ≥ LLOQ at the Final Treatment Visit were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With Post-Treatment Relapse12 | 1.2 percentage of participants |
Other Pre-specified
Percentage of Female Participants Responding With SVR12: mITT-GT Population
SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: 12 weeks after the last actual dose of study drug
Population: The mITT-GT population includes participants who received at least 1 dose of study drug but excludes the participants who do not have HCV GT1b infection; female participants. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Female Participants Responding With SVR12: mITT-GT Population | 97.8 percentage of participants |
Other Pre-specified
Percentage of Participants Who Achieve SVR12: mITT-GT Population
SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: 12 weeks after the last actual dose of study drug
Population: The modified ITT (mITT)-GT population includes participants who received at least 1 dose of study drug but excludes the participants who do not have HCV GT1b infection. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants Who Achieve SVR12: mITT-GT Population | 98.2 percentage of participants |
Other Pre-specified
Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12: mITT-GT Population
SVR12 is defined as HCV RNA \< LLOQ 12 weeks after the last dose of study drugs without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: Baseline and 12 weeks after the last actual dose of study drug
Population: The mITT-GT population includes participants who received at least 1 dose of study drug but excludes the participants who do not have HCV GT1b infection; participants with baseline HCV RNA \< 6,000,000 IU/mL. Flanking imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With Baseline HCV RNA < 6,000,000 IU/mL Responding With SVR12: mITT-GT Population | 98.7 percentage of participants |
Other Pre-specified
Percentage of Participants With On-Treatment Virologic Failure During Treatment Period: mITT-GT Population
On-treatment virologic failure is defined as breakthrough (confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir in HCV RNA (two consecutive HCV rna measurements \> 1 log\^10 IU/mL above nadir) at any time point during treatment) or failure to suppress during treatment (all on-treatment values of HCV RNA ≥ LLOQ) with at least 6 weeks (defined as study drug duration ≥ 36 days) of treatment. Confidence interval calculated using the Wilson score method.
Time frame: Up to 8 weeks while on treatment
Population: The mITT-GT population includes participants who received at least 1 dose of study drug but excludes the participants who do not have HCV GT1b infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With On-Treatment Virologic Failure During Treatment Period: mITT-GT Population | 0 percentage of participants |
Other Pre-specified
Percentage of Participants With Post-Treatment Relapse12: mITT-GT Population
Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of active study drug (up to and including the SVR12 window) excluding reinfection among participants with HCV RNA \< LLOQ at final treatment visit who complete treatment and have post-treatment HCV RNA data. Completion of treatment is defined as a study drug duration ≥ 51 days for participants who receive 8 weeks of treatment. HCV reinfection is defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at final treatment visit, along with the post treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences. Confidence interval calculated using the normal approximation to the binomial distribution.
Time frame: Up to 12 weeks after last dose of study drug
Population: The mITT-GT population includes participants who received at least 1 dose of study drug but excludes the participants who do not have HCV GT1b infection. Participants who did not complete treatment or had no post treatment data available or had HCV RNA ≥ LLOQ at the Final Treatment Visit were not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir | Percentage of Participants With Post-Treatment Relapse12: mITT-GT Population | 1.2 percentage of participants |