Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C Virus, Hepatitis C Genotype 1, Hepatitis C, Treatment-Naïve, Interferon-Free, Chronic Hepatitis C, Viekira Pak, ombitasvir, paritaprevir, dasabuvir
Brief summary
The purpose of this study is to evaluate the safety and efficacy of ABT-450, ritonavir and ABT-267 (ABT-450/r/ABT-267; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) co-administered with ribavirin (RBV) in hepatitis C virus genotype 1 infected treatment-naïve adults.
Interventions
Capsule
ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
DRUGRibavirin
Capsule (double-blind treatment period), tablet (open-label treatment period)
Tablet
Tablet
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Females must be post-menopausal for at least 2 years or surgically sterile or practicing specific forms of birth control * Chronic hepatitis C, genotype 1-infection and HCV RNA level greater than 10,000 IU/mL at screening * Subject has never received antiviral treatment for hepatitis C infection * No evidence of liver cirrhosis
Exclusion criteria
* Positive screen for drugs or alcohol * Significant sensitivity to any drug * Use of contraindicated medications within 2 weeks of dosing * Certain predefined abnormal laboratory tests * Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment | 12 weeks after the last actual dose of active study drug | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period | At 12 weeks | Normalization is defined as alanine aminotransferase less than or equal to the upper limit of normal (ULN) at final treatment visit for participants with alanine aminotransferase greater than ULN at baseline. |
| Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After Treatment | 12 weeks after the last actual dose of active study drug | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. |
| Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After Treatment | 12 weeks after the last actual dose of active study drug | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. |
| Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | 12 weeks after the last actual dose of active study drug | Virologic failure was defined as rebound (hepatitis C virus ribonucleic acid \[HCV RNA\] ≥ lower limit of quantification \[LLOQ\] after HCV RNA \< LLOQ or increase in HCV RNA of at least 1 log10 IU/mL) or failure to suppress (all on-treatment values of plasma HCV RNA ≥ LLOQ with at least 36 days of treatment) during treatment. |
| Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | Within 12 weeks post-treatment | Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA \< LLOQ at the end of treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 473 |
| Placebo Double-blind placebo for 12 weeks | 158 |
| Total | 631 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment | Adverse Event | 2 | 1 |
| Double-blind Treatment | Did Not Receive Study Drug | 4 | 1 |
| Double-blind Treatment | Lost to Follow-up | 2 | 0 |
| Double-blind Treatment | Other | 1 | 0 |
| Double-blind Treatment | Subject Noncompliant | 1 | 0 |
| Double-blind Treatment | Withdrawal by Subject | 3 | 0 |
| Open-label Treatment | Adverse Event | 0 | 2 |
| Open-label Treatment | Virologic Failure | 0 | 2 |
| Open-label Treatment | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Total | ABT-450/r/ABT-267 and ABT-333, Plus RBV | Placebo |
|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 10.82 | 49.4 years STANDARD_DEVIATION 10.98 | 51.2 years STANDARD_DEVIATION 10.23 |
| Sex: Female, Male Female | 287 Participants | 202 Participants | 85 Participants |
| Sex: Female, Male Male | 344 Participants | 271 Participants | 73 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 | 391 / 473 | 108 / 158 | 117 / 157 |
| serious Total, serious adverse events | 10 / 473 | 0 / 158 | 2 / 157 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last actual dose of active study drug
Population: Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment | 96.4 percentage of participants |
Comparison: With a sample size of 450 subjects and assuming that 92% of the subjects in Arm A will achieve SVR12, this study has greater than 90% power to demonstrate non-inferiority with a 2-sided 95% lower confidence bound greater than 70% and greater than 90% power to demonstrate superiority with a 2-sided 95% lower confidence bound greater than 80% (based on the normal approximation of a single binomial proportion). 95% CI calculated using the normal approximation to the binomial distribution.95% CI: [94.7, 98.1]
Secondary
Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After Treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last actual dose of active study drug
Population: Intent-to-treat (ITT) Population: All randomized participants in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm with HCV genotype 1a who received at least 1 dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After Treatment | 95.7 percentage of participants |
95% CI: [93.4, 97.9]
Secondary
Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After Treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last actual dose of active study drug
Population: Intent-to-treat (ITT) Population: All randomized participants in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm with HCV genotype 1b who received at least 1 dose of blinded study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After Treatment | 98.0 percentage of participants |
95% CI: [95.8, 100]
Secondary
Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period
Normalization is defined as alanine aminotransferase less than or equal to the upper limit of normal (ULN) at final treatment visit for participants with alanine aminotransferase greater than ULN at baseline.
Time frame: At 12 weeks
Population: Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug and had ALT ≥ ULN of the reference range at baseline were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period | 97.0 percentage of participants |
| Placebo | Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period | 15.8 percentage of participants |
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm
Virologic failure was defined as rebound (hepatitis C virus ribonucleic acid \[HCV RNA\] ≥ lower limit of quantification \[LLOQ\] after HCV RNA \< LLOQ or increase in HCV RNA of at least 1 log10 IU/mL) or failure to suppress (all on-treatment values of plasma HCV RNA ≥ LLOQ with at least 36 days of treatment) during treatment.
Time frame: 12 weeks after the last actual dose of active study drug
Population: Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | 0.2 percentage of participants |
Secondary
Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm
Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA \< LLOQ at the end of treatment.
Time frame: Within 12 weeks post-treatment
Population: Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug with HCV RNA \< LLOQ at the final treatment visit who completed treatment in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | 1.5 percentage of participants |