Chronic Hepatitis C Infection
Conditions
Keywords
Chronic Hepatitis C, Hepatitis C Treatment Naive, Hepatitis C Genotype 1, Hepatitis C Treatment Experienced, Hepatitis C Virus
Brief summary
The purpose of this study is to evaluate the proportion of subjects achieving sustained virologic response 12 weeks post-treatment (SVR12) in adults with genotype 1 (GT1) chronic HCV infection, who received treatment with 3 direct-acting antiviral agents (3-DAAs; ombitasvir/paritaprevir/ritonavir and dasabuvir) with or without ribavirin.
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
* Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control * Males must be surgically sterile or agree to practice acceptable forms of birth control * Chronic hepatitis C virus (HCV) infection at screening * Fibrosis stage F3 or greater, documented by acceptable tests * Participants with cirrhosis: Absence of hepatocellular carcinoma (HCC) as indicated by acceptable methods
Exclusion criteria
* Women who are pregnant or breastfeeding * Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibody positive (HIV Ab) * Use of contraindicated medications within 2 weeks of dosing * Clinically significant abnormalities or co-morbidities * History of solid organ transplant * Abnormal laboratory tests * Current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation
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. Participants with missing data were counted as failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 12 weeks after the last actual dose of study drug | SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' prior HCV treatment experience at screening. Participants with missing data were counted as failures. |
| Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening | 12 weeks after the last actual dose of study drug | SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' eligibility for treatment with IFN at screening. Participants with missing data were counted as failures. |
| Percentage of Participants With SVR12 by Fibrosis Stage | 12 weeks after the last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ\]12 weeks after the last dose of study drug. The percentage of participants achieving SVR12 by fibrosis stage (F3 and F4) are presented. Participants with missing data were counted as failures. |
| Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | Day 1 (Baseline), 12 weeks after the last actual dose of the study drug | The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain |
| (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | Day 1 (Baseline), 12 weeks after the last actual dose of the study drug | The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a PCS score and a MCS score. Scores SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain was missing. |
| Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | Day 1 (Baseline), 12 weeks after the last actual dose of the study drug | The HCV-PRO has been developed to capture the function and well-being impact of HCV conditions and treatment and contains 16 items important to HCV-infected patients; items were totaled to a summary score. Scores range from 0 to 100. A higher HCV-PRO score indicates a better state of health and a decrease from baseline represents worsening. If a participant answered at least 12 of the 16 items, the missing items were imputed with the mean score of the answered items; if a participant did not answer at least 12 of the items, the total score was considered missing. |
Participant flow
Pre-assignment details
Treatment regimen was assigned according to HCV genotype/subtype and cirrhosis status.
Participants by arm
| Arm | Count |
|---|---|
| 3-DAA ± RBV 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks. | 222 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Withdrew Consent | 1 |
Baseline characteristics
| Characteristic | 3-DAA ± RBV |
|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 10.34 |
| Sex: Female, Male Female | 99 Participants |
| Sex: Female, Male Male | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 139 / 222 |
| serious Total, serious adverse events | 6 / 222 |
Outcome results
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. Participants with missing data were counted as failures.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA ± RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 96.4 percentage of participants |
Secondary
Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
The HCV-PRO has been developed to capture the function and well-being impact of HCV conditions and treatment and contains 16 items important to HCV-infected patients; items were totaled to a summary score. Scores range from 0 to 100. A higher HCV-PRO score indicates a better state of health and a decrease from baseline represents worsening. If a participant answered at least 12 of the 16 items, the missing items were imputed with the mean score of the answered items; if a participant did not answer at least 12 of the items, the total score was considered missing.
Time frame: Day 1 (Baseline), 12 weeks after the last actual dose of the study drug
Population: All participants in the ITT population with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3-DAA ± RBV | Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | 0.5 units on a scale | Standard Deviation 10.97 |
| 3-DAA ± RBV | Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 3.8 units on a scale | Standard Deviation 13.25 |
| Fibrosis Stage F4 | Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | 0.8 units on a scale | Standard Deviation 10.64 |
| Fibrosis Stage F4 | Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 4.2 units on a scale | Standard Deviation 15.72 |
Secondary
Percentage of Participants With SVR12 by Fibrosis Stage
SVR12 was defined as plasma HCV RNA level \<LLOQ\]12 weeks after the last dose of study drug. The percentage of participants achieving SVR12 by fibrosis stage (F3 and F4) are presented. Participants with missing data were counted as failures.
Time frame: 12 weeks after the last actual dose of study drug
Population: All participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA ± RBV | Percentage of Participants With SVR12 by Fibrosis Stage | 96.6 percentage of participants |
| Fibrosis Stage F4 | Percentage of Participants With SVR12 by Fibrosis Stage | 96.2 percentage of participants |
Secondary
Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening
SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' eligibility for treatment with IFN at screening. Participants with missing data were counted as failures.
Time frame: 12 weeks after the last actual dose of study drug
Population: All participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA ± RBV | Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening | 90.0 percentage of participants |
| Fibrosis Stage F4 | Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening | 96.7 percentage of participants |
| Pegylated Interferon (PegIFN)//RBV Partial Responders | Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening | 85.7 percentage of participants |
| Pegylated Interferon (PegIFN)/RBV Non-Responders | Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening | 97.3 percentage of participants |
Secondary
Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience
SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' prior HCV treatment experience at screening. Participants with missing data were counted as failures.
Time frame: 12 weeks after the last actual dose of study drug
Population: All participants in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3-DAA ± RBV | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 96.1 percentage of participants |
| Fibrosis Stage F4 | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 95.5 percentage of participants |
| Pegylated Interferon (PegIFN)//RBV Partial Responders | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 100 percentage of participants |
| Pegylated Interferon (PegIFN)/RBV Non-Responders | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 100 percentage of participants |
| Pegylated Interferon (PegIFN)/RBV Relapser | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 97.1 percentage of participants |
| Pegylated Interferon (PegIFN)/RBV Breakthrough | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 100 percentage of participants |
| IFN Interolerant | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 85.7 percentage of participants |
| Other | Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience | 91.7 percentage of participants |
Secondary
(SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a PCS score and a MCS score. Scores SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain was missing.
Time frame: Day 1 (Baseline), 12 weeks after the last actual dose of the study drug
Population: All participants in the ITT population with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3-DAA ± RBV | (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | 2.4 units on a scale | Standard Deviation 3.72 |
| 3-DAA ± RBV | (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 2.4 units on a scale | Standard Deviation 11.39 |
| Fibrosis Stage F4 | (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | -0.6 units on a scale | Standard Deviation 8.47 |
| Fibrosis Stage F4 | (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 2.5 units on a scale | Standard Deviation 9.15 |
Secondary
Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain
Time frame: Day 1 (Baseline), 12 weeks after the last actual dose of the study drug
Population: All participants in the ITT population with evaluable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 3-DAA ± RBV | Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | -0.5 units on a scale | Standard Deviation 9.22 |
| 3-DAA ± RBV | Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 0.1 units on a scale | Standard Deviation 6.42 |
| Fibrosis Stage F4 | Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Not Achieved | 1.3 units on a scale | Standard Deviation 8.59 |
| Fibrosis Stage F4 | Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug | SVR12 Achieved | 2.1 units on a scale | Standard Deviation 7.6 |