Chronic Hepatitis C Infection
Conditions
Keywords
Chronic Hepatitis C, Interferon Free, Hepatitis C Treatment Naive, Hepatitis C Virus, Hepatitis C Genotype 1
Brief summary
This is a study to evaluate the efficacy and safety of three experimental drugs compared with telaprevir (a licensed product) in people with hepatitis C virus infection who have not had treatment before.
Detailed description
The primary purpose of this study is to demonstrate that treatment with ABT-450/ritonavir (r)/ABT-267 and ABT-333 administered with or without ribavirin (RBV) has non-inferior efficacy compared to treatment with telaprevir and pegylated interferon alpha-2a (pegIFN) and RBV and to compare the safety of these regimens in treatment-naive hepatitis C virus (HCV) genotype (GT) 1a- and 1b-infected adults.
Interventions
DRUGRibavirin
Tablet
DRUGTelaprevir
Film-coated tablet
DRUGPegylated Interferon alpha 2-a (PegIFN)
Pre-filled syringe
Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males or females between 18 and 65 years, inclusive, at time of Screening * Females must be post-menopausal for more than 2 years or surgically sterile or practicing abstinence/specific forms of birth control * Subject has never received antiviral treatment for hepatitis C infection * Chronic HCV Genotype-1 infection prior to study enrollment
Exclusion criteria
* Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) * Females who are pregnant or plan to become pregnant, or breastfeeding * Any current or past clinical evidence of cirrhosis * Screening laboratory analyses that showing abnormal laboratory results * Use of contraindicated medications within 2 weeks of dosing and subject with contraindication for telaprevir, pegIFN and RBV * Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol * Positive screen for drugs or alcohol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 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 |
|---|---|---|
| Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E | SF-36V2 is a generic 36-item questionnaire measuring HRQoL covering 2 summary measures: PCS and MCS; it consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, bodily pain, and general health perception. Participants self-report on items in a subscale that have choices per item. Scoring is done for both PCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL). |
| Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 12 weeks after the last actual dose of active study drug | The percentage of participants with sustained virologic response (plasma HCV RNA level \< LLOQ) 12 weeks after the last dose of study drug. |
| Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E | SF-36V2 is a generic 36-item questionnaire measuring health-related quality of life (HRQoL) covering 2 summary measures: physical component summary (PCS) and MCS; it consists of 8 subscales. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have choices per item. Scoring is done for both MCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL). |
| Percentage of Participants With Post-treatment Relapse | Within 24 weeks post treatment | Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 24 weeks post treatment among participants completing treatment and with HCV RNA less than the LLOQ at the end of treatment. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 24 weeks after the last actual dose of active study drug | The percentage of participants with sustained virologic response (plasma HCV RNA level \< LLOQ) 24 weeks after the last dose of study drug. |
| Percentage of Participants With Virologic Failure During Treatment | 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E | Participants in Arms A, C or D demonstrating any of the following were considered virologic failures and discontinued therapy: * Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of \>1 log10 IU/mL above nadir) at any time point during treatment * Failure to achieve HCV RNA \< LLOQ by Week 6 or * Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA \< LLOQ during treatment after HCV RNA \< LLOQ. Participants in Arms B and E followed virologic stopping criteria described in the TPV Summary of Product Characteristics; they were considered virologic failures and discontinued therapy as follows: * HCV RNA \> 1000 IU/mL at Week 4 to Week 12, discontinue TPV and pegIFN and RBV * HCV RNA \> 1000 IU/mL at Week 12, discontinue pegIFN and RBV * Confirmed HCV RNA \> lower limit of detection (LLOD) at Week 24, discontinue pegIFN and RBV * Confirmed HCV RNA \> LLOD at Week 36, discontinue pegIFN and RBV. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 3-DAA + RBV in GT1a ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID and weight-based RBV for 12 weeks (3 DAAs with RBV in GT1a) | 69 |
| Arm B: TPV/PR in GT1a TPV 750 mg q8h and pegIFN 180 µg/week and weight-based RBV for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1a) | 34 |
| Arm C: 3-DAA + RBV in GT1b ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID and weight-based RBV for 12 weeks (3 DAAs with RBV in GT1b) | 84 |
| Arm D: 3-DAA in GT1b ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID for 12 weeks (3 DAAs without RBV in GT1b) | 83 |
| Arm E: TPV/PR in GT1b Telaprevir 750 mg q8h and pegIFN 180 µg/week and weight-based RBV for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1b) | 41 |
| Total | 311 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 1 | 1 | 2 | 0 |
| Overall Study | Other | 0 | 1 | 1 | 0 | 0 |
| Overall Study | To enter another AbbVie study | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew Consent | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm E: TPV/PR in GT1b | Total | Arm A: 3-DAA + RBV in GT1a | Arm B: TPV/PR in GT1a | Arm C: 3-DAA + RBV in GT1b | Arm D: 3-DAA in GT1b |
|---|---|---|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 10.78 | 46.2 years STANDARD_DEVIATION 11.75 | 46.1 years STANDARD_DEVIATION 12.25 | 44.5 years STANDARD_DEVIATION 14.1 | 46.2 years STANDARD_DEVIATION 11.34 | 47.1 years STANDARD_DEVIATION 11.33 |
| Age, Customized < 55 years | 31 participants | 219 participants | 46 participants | 23 participants | 59 participants | 60 participants |
| Age, Customized >= 55 years | 10 participants | 92 participants | 23 participants | 11 participants | 25 participants | 23 participants |
| Sex: Female, Male Female | 24 Participants | 151 Participants | 21 Participants | 17 Participants | 46 Participants | 43 Participants |
| Sex: Female, Male Male | 17 Participants | 160 Participants | 48 Participants | 17 Participants | 38 Participants | 40 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 | 100 / 153 | 29 / 83 | 74 / 75 |
| serious Total, serious adverse events | 1 / 153 | 0 / 83 | 9 / 75 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses
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 Population: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 97.1 percentage of participants |
| Arm B: TPV/PR in GT1a | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 82.4 percentage of participants |
| Arm C: 3-DAA + RBV in GT1b | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 98.8 percentage of participants |
| Arm D: 3-DAA in GT1b | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 97.6 percentage of participants |
| Arm E: TPV/PR in GT1b | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) - Primary Efficacy Analyses | 78.0 percentage of participants |
95% CI: [1.3, 28.2]
95% CI: [6.4, 32.6]
Secondary
Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS)
SF-36V2 is a generic 36-item questionnaire measuring HRQoL covering 2 summary measures: PCS and MCS; it consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, bodily pain, and general health perception. Participants self-report on items in a subscale that have choices per item. Scoring is done for both PCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL).
Time frame: From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E
Population: Intent-to-treat Population: all randomized participants who received at least 1 dose of study drug and a baseline and post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | 0.5 units on a scale | Standard Deviation 8.63 |
| Arm B: TPV/PR in GT1a | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | -5.5 units on a scale | Standard Deviation 8.26 |
| Arm C: 3-DAA + RBV in GT1b | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | 0.4 units on a scale | Standard Deviation 5.8 |
| Arm D: 3-DAA in GT1b | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | 2.2 units on a scale | Standard Deviation 4.34 |
| Arm E: TPV/PR in GT1b | Mean Change From Baseline to the Final Treatment Visit in SF-36V2 Physical Component Summary (PCS) | -5.5 units on a scale | Standard Deviation 11.46 |
p-value: <0.00195% CI: [2.72, 9.44]ANCOVA
p-value: <0.00195% CI: [3.55, 8.85]ANCOVA
p-value: <0.00195% CI: [4.36, 9.37]ANCOVA
Secondary
Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS)
SF-36V2 is a generic 36-item questionnaire measuring health-related quality of life (HRQoL) covering 2 summary measures: physical component summary (PCS) and MCS; it consists of 8 subscales. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have choices per item. Scoring is done for both MCS subscale scores and summary scores; for each, the range is 0 (worst HRQoL) to 100 (best HRQoL).
Time frame: From Day 1 of treatment up to 12 weeks for Arms A, C and D and up to 24 or 48 weeks for Arms B and E
Population: Intent-to-treat Population: all randomized participants who received at least 1 dose of study drug and a baseline and post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | -4.2 units on a scale | Standard Deviation 10.59 |
| Arm B: TPV/PR in GT1a | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | -5.8 units on a scale | Standard Deviation 12.18 |
| Arm C: 3-DAA + RBV in GT1b | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | -0.3 units on a scale | Standard Deviation 8.89 |
| Arm D: 3-DAA in GT1b | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | -0.1 units on a scale | Standard Deviation 7.73 |
| Arm E: TPV/PR in GT1b | Mean Change From Baseline to the Final Treatment Visit in Short-Form 36 Version 2 Health Status Survey (SF-36V2) Mental Component Summary (MCS) | -6.4 units on a scale | Standard Deviation 11.78 |
p-value: 0.35195% CI: [-2.39, 6.65]ANCOVA
p-value: 0.00295% CI: [2.19, 9.47]ANCOVA
p-value: 0.00295% CI: [2.01, 8.54]ANCOVA
Secondary
Percentage of Participants With Post-treatment Relapse
Hepatitis C virus (HCV) ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (LLOQ) between the end of treatment and 24 weeks post treatment among participants completing treatment and with HCV RNA less than the LLOQ at the end of treatment.
Time frame: Within 24 weeks post treatment
Population: Intent-to-treat Population: all randomized participants who received at least 1 dose of study drug and had sustained virologic response at Week 24 (SVR24).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm B: TPV/PR in GT1a | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm C: 3-DAA + RBV in GT1b | Percentage of Participants With Post-treatment Relapse | 1.2 percentage of participants |
| Arm D: 3-DAA in GT1b | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm E: TPV/PR in GT1b | Percentage of Participants With Post-treatment Relapse | 6.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
The percentage of participants with sustained virologic response (plasma HCV RNA level \< LLOQ) 24 weeks after the last dose of study drug.
Time frame: 24 weeks after the last actual dose of active study drug
Population: Intent-to-treat Population: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 95.7 percentage of participants |
| Arm B: TPV/PR in GT1a | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 82.4 percentage of participants |
| Arm C: 3-DAA + RBV in GT1b | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 97.6 percentage of participants |
| Arm D: 3-DAA in GT1b | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 97.6 percentage of participants |
| Arm E: TPV/PR in GT1b | Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | 78.0 percentage of participants |
95% CI: [-0.4, 27]
95% CI: [6.5, 32.7]
95% CI: [6.4, 32.6]
Secondary
Percentage of Participants With SVR12 - Secondary Efficacy Analyses
The percentage of participants with sustained virologic response (plasma HCV RNA level \< 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 Population: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 97.1 percentage of participants |
| Arm B: TPV/PR in GT1a | Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 82.4 percentage of participants |
| Arm C: 3-DAA + RBV in GT1b | Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 98.8 percentage of participants |
| Arm D: 3-DAA in GT1b | Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 97.6 percentage of participants |
| Arm E: TPV/PR in GT1b | Percentage of Participants With SVR12 - Secondary Efficacy Analyses | 78.0 percentage of participants |
p-value: 0.02195% CI: [1.4, 38]Regression, Logistic
95% CI: [7.9, 33.6]
p-value: 0.00295% CI: [3.3, 241.1]Regression, Logistic
p-value: 0.005Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Virologic Failure During Treatment
Participants in Arms A, C or D demonstrating any of the following were considered virologic failures and discontinued therapy: * Confirmed increase from nadir in HCV RNA (defined as 2 consecutive HCV RNA measurements of \>1 log10 IU/mL above nadir) at any time point during treatment * Failure to achieve HCV RNA \< LLOQ by Week 6 or * Confirmed HCV RNA ≥ LLOQ (defined as 2 consecutive HCV RNA measurements ≥ LLOQ) at any point after HCV RNA \< LLOQ during treatment after HCV RNA \< LLOQ. Participants in Arms B and E followed virologic stopping criteria described in the TPV Summary of Product Characteristics; they were considered virologic failures and discontinued therapy as follows: * HCV RNA \> 1000 IU/mL at Week 4 to Week 12, discontinue TPV and pegIFN and RBV * HCV RNA \> 1000 IU/mL at Week 12, discontinue pegIFN and RBV * Confirmed HCV RNA \> lower limit of detection (LLOD) at Week 24, discontinue pegIFN and RBV * Confirmed HCV RNA \> LLOD at Week 36, discontinue pegIFN and RBV.
Time frame: 12 weeks for Arms A, C and D and 24 weeks or 48 weeks for Arms B and E
Population: Intent-to-treat Population: all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 3-DAA + RBV in GT1a | Percentage of Participants With Virologic Failure During Treatment | 2.9 percentage of participants |
| Arm B: TPV/PR in GT1a | Percentage of Participants With Virologic Failure During Treatment | 5.9 percentage of participants |
| Arm C: 3-DAA + RBV in GT1b | Percentage of Participants With Virologic Failure During Treatment | 0 percentage of participants |
| Arm D: 3-DAA in GT1b | Percentage of Participants With Virologic Failure During Treatment | 1.2 percentage of participants |
| Arm E: TPV/PR in GT1b | Percentage of Participants With Virologic Failure During Treatment | 12.2 percentage of participants |