Chronic Hepatitis C Infection
Conditions
Keywords
Japanese, Hepatitis C, Genotype 2, Genotype 1b, paritaprevir, ombitasvir, ritonavir, VIEKIRAX Combination Tablets
Brief summary
This study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adult Japanese patients with chronic hepatitis C virus genotype 1b (HCV GT1b) or genotype 2 (HCV GT2) infection who were previous treated with pegylated interferon/ribavirin (pegIFN/RBV).
Detailed description
This multicenter, randomized, open-label, parallel-arm, combination treatment study consisted of a Treatment and Post-treatment Phase, divided into 2 cohorts: 1) chronic HCV GT1b- infected, pegIFN/RBV treatment-exposed Japanese adults; and 2) HCV GT2-infected, pegIFN/RBV treatment-exposed Japanese adults. The Treatment Phase evaluated the antiviral activity, safety, and pharmacokinetics of a range of ABT-450/r and ABT-267 doses for 12 to 24 weeks. The Post-treatment Phase evaluated the evolution and persistence of viral resistance to ABT-267 and ABT-450.
Interventions
DRUGABT-450/ritonavir, ABT-267
ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile * Chronic hepatitis C, genotype 1b (HCV-GT1b) or genotype 2 (HCV GT2) infection (HCV RNA level greater than 10,000 IU/mL at screening) previously treated with pegylated interferon/ribavirin (pegIFN/RBV). * Subject's hepatitis C virus genotype is subgenotype 1b and subject was a null responder or partial responder, OR * Subject's hepatitis C virus genotype is subgenotype 2 and subject was a null responder, partial responder, or relapser (Null responder: received at least 10 weeks of pegIFN/RBV for the treatment of HCV and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12; Partial responders: received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved ≥ 2 log10 IU/mL reduction in HCV RNA at Week 12, but failed to achieve HCV RNA undetectable (HCV RNA \< lower limit of detection \[\< LLOD\]) at the end of treatment; Relapsers: received at least 1 course of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 24 weeks of treatment follow-up).
Exclusion criteria
* Significant liver disease with any cause other than HCV as the primary cause * Positive screen for drugs or alcohol. * Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody. * Use of contraindicated medications within 2 weeks of dosing * Previous use of any investigational or commercially available anti-Hepatitis C virus agent other than pegIFN/RBV, including previous exposure to ABT-450 or ABT-267.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 24 weeks after last dose of study drug | The percentage of participants with SVR24 (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\] 24 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL. |
| Number of Participants With Adverse Events (AEs) | TEAEs: up to 16 weeks for the 12-week treatment groups and up to 28 weeks for the 24-week treatment groups; SAEs: up to 65 weeks for the 12-week treatment groups and up to 77 weeks for the 24-week treatment groups. | An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 12 weeks after last dose of study drug | The percentage of participants with SVR12 (plasma HCV RNA level \< LLOQ 12 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL. |
| Percentage of Participants With End of Treatment (EOT) Response | 12 or 24 weeks after first dose of study drug | The percentage of participants with EOT response (plasma HCV RNA level \< LLOQ at week 12 for the 12-week duration arms and Week 24 for the 24-week duration arms12). The LLOQ for the assay was 25 IU/mL. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | 18 |
| Arm 2 Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | 18 |
| Arm 3 Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. | 19 |
| Arm 4 Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. | 18 |
| Arm 5 Participants with HCV GT2 received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | 19 |
| Arm 6 Participants with HCV GT2 received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | 18 |
| Total | 110 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Arm 3 | Arm 4 | Arm 5 | Arm 6 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 15.06 | 54.8 years STANDARD_DEVIATION 11.96 | 61.9 years STANDARD_DEVIATION 8.14 | 57.5 years STANDARD_DEVIATION 10.15 | 62.5 years STANDARD_DEVIATION 8.34 | 62.8 years STANDARD_DEVIATION 7.89 | 59.2 years STANDARD_DEVIATION 10.84 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 12 Participants | 10 Participants | 12 Participants | 10 Participants | 59 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 7 Participants | 8 Participants | 7 Participants | 8 Participants | 51 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 18 | 15 / 18 | 16 / 19 | 15 / 18 | 14 / 19 | 16 / 18 |
| serious Total, serious adverse events | 0 / 18 | 2 / 18 | 2 / 19 | 0 / 18 | 1 / 19 | 0 / 18 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose.
Time frame: TEAEs: up to 16 weeks for the 12-week treatment groups and up to 28 weeks for the 24-week treatment groups; SAEs: up to 65 weeks for the 12-week treatment groups and up to 77 weeks for the 24-week treatment groups.
Population: Safety population: all participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 | Number of Participants With Adverse Events (AEs) | Adverse Events | 28 participants |
| Arm 1 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events | 1 participants |
| Arm 2 | Number of Participants With Adverse Events (AEs) | Adverse Events | 31 participants |
| Arm 2 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events | 2 participants |
| Arm 3 | Number of Participants With Adverse Events (AEs) | Adverse Events | 16 participants |
| Arm 3 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events | 2 participants |
| Arm 4 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events | 0 participants |
| Arm 4 | Number of Participants With Adverse Events (AEs) | Adverse Events | 15 participants |
Primary
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
The percentage of participants with SVR24 (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\] 24 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
Time frame: 24 weeks after last dose of study drug
Population: Intent-to-treat (ITT) population: all subjects who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 100 percentage of participants |
| Arm 2 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 88.9 percentage of participants |
| Arm 3 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 100 percentage of participants |
| Arm 4 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 100 percentage of participants |
| Arm 5 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 57.9 percentage of participants |
| Arm 6 | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 72.2 percentage of participants |
Secondary
Percentage of Participants With End of Treatment (EOT) Response
The percentage of participants with EOT response (plasma HCV RNA level \< LLOQ at week 12 for the 12-week duration arms and Week 24 for the 24-week duration arms12). The LLOQ for the assay was 25 IU/mL.
Time frame: 12 or 24 weeks after first dose of study drug
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With End of Treatment (EOT) Response | 100 percentage of participants |
| Arm 2 | Percentage of Participants With End of Treatment (EOT) Response | 100 percentage of participants |
| Arm 3 | Percentage of Participants With End of Treatment (EOT) Response | 100 percentage of participants |
| Arm 4 | Percentage of Participants With End of Treatment (EOT) Response | 100 percentage of participants |
| Arm 5 | Percentage of Participants With End of Treatment (EOT) Response | 63.2 percentage of participants |
| Arm 6 | Percentage of Participants With End of Treatment (EOT) Response | 83.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12)
The percentage of participants with SVR12 (plasma HCV RNA level \< LLOQ 12 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
Time frame: 12 weeks after last dose of study drug
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 100 percentage of participants |
| Arm 2 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 88.9 percentage of participants |
| Arm 3 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 100 percentage of participants |
| Arm 4 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 100 percentage of participants |
| Arm 5 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 57.9 percentage of participants |
| Arm 6 | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | 72.2 percentage of participants |