Hepatitis C Virus Infection
Conditions
Keywords
Chronic Hepatitis C (HCV), HCV Genotype 1 (HCV GT1), HCV Genotype 2 (HCV GT2), HCV Genotype 3 (HCV GT3), HCV Genotype 4 (HCV GT4), HCV Genotype 5 (HCV GT5), HCV Genotype 6 (HCV GT6), Compensated Cirrhosis, Non-cirrhotics, Virologic failure
Brief summary
The purpose of this study was to evaluate the efficacy and safety of co-administration of glecaprevir (ABT-493)/pibrentasvir (ABT 530) plus sofosbuvir (SOF) plus ribavirin (RBV) in hepatitis C virus (HCV) genotype (GT) 1 - 6-infected participants (including non-cirrhotic, or cirrhotic with compensated cirrhosis participants) who had experienced virologic failure in an AbbVie parent clinical study.
Detailed description
This study enrolled HCV infected adults who had experienced virologic failure following treatment with glecaprevir/pibrentasvir or paritaprevir/ritonavir/ombitasvir + dasabuvir (DSV) (3D) or paritaprevir/ritonavir/ombitasvir (2D) regimens in one of the following AbbVie hepatitis C virus parent studies: * M13-594 (NCT02640157) * M13-596 (NCT02692703) * M14-172 (NCT02642432) * M14-242 (NCT02493855) * M14-868 (NCT02243293) * M15-410 (NCT02446717) * M15-592 (NCT03222583) * M16-126 (NCT02966795) * M16-135 (NCT03089944)
Interventions
DRUGSofosbuvir
Tablet for oral administration
Coformulated tablet for oral administration
DRUGRibavirin
Tablet for oral administration
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects must be adults (18 years of age or older) or adolescents (12 to less than 18 years of age weighing at least 35 kg). * Subject must have experienced virologic failure during or after treatment with ABT-493/ABT-530 in an AbbVie HCV parent study. Subjects who have experienced virologic failure during or after receiving ombitasvir/paritaprevir/r + dasabuvir (3D), or ombitasvir/paritaprevir/r (2D) in an AbbVie HCV parent study may be enrolled at AbbVie's discretion. Treatment in the parent study must have been completed or discontinued at least 1 month prior to the Screening Visit. * Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements. * Cirrhotic subjects must have compensated cirrhosis, (Child-Pugh score of ≤ 6) at Screening and no current or past evidence of Child-Pugh B or C Classification or no clinical history of liver decompensation, including ascites noted on physical exam, hepatic encephalopathy or esophageal variceal bleeding. * Cirrhotic subjects must have absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound (US), computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or a negative US at Screening.
Exclusion criteria
* History of severe, life-threatening or other clinically significant sensitivity to any study drug or drug component. * Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for 4 months after the last dose of study drug, or as directed per the local RBV label, whichever is more restrictive. * Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. * Positive test result at Screening for hepatitis B surface antigen (HBsAg). * Screening laboratory analyses showing calculated creatinine clearance \< 30 mL/min. * Discontinuation from the AbbVie HCV parent study for reasons other than virologic failure (e.g., non-adherence, lost to follow-up, and/or the occurrence of an adverse event). * Receipt of any HCV treatment after failing the treatment regimen in the AbbVie HCV parent study.
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, Week 24 or Week 28 depending on the treatment regimen. | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | 12 or 16 weeks depending on the treatment regimen | On-treatment virologic failure was defined as meeting one of the following: * confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir) at any time point during the treatment period; or * confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA \< 15 IU/mL during the treatment period, or * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen). | Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< 15 IU/mL at the end of treatment, and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed. |
Countries
Australia, Canada, China, Germany, New Zealand, Russia, South Korea, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Participants with hepatitis C virus (HCV) genotypes (GT) 1-6 infection who had virologic failure while participating in an AbbVie HCV Parent Study were enrolled at 26 sites in 12 countries.
Pre-assignment details
Participants were allocated to 1 of 2 treatment arms based on HCV GT, cirrhosis status, and treatment experience with protease inhibitor (PI) and/or nonstructural viral protein 5A protease inhibitor (NS5Ai)-containing regimens prior to enrolling in the AbbVie HCV Parent Study.
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks Participants without cirrhosis who had non-genotype 3 infection and were naïve to PI and/or NS5Ai prior to participation in AbbVie HCV parent study received daily treatment with GLE/PIB 300 mg/120 mg plus SOF 400 mg plus twice-daily weight-based RBV 600 mg - 1200 mg daily total for 12 weeks. | 5 |
| Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks Participants with genotype 3, and/or compensated cirrhosis, and/or experience with PI and/or NS5Ai prior to participation in Abbvie HCV parent study received daily treatment with GLE/PIB 300 mg/120 mg plus SOF 400 mg plus twice-daily weight-based RBV 600 mg - 1200 mg daily total for 16 weeks. | 28 |
| Total | 33 |
Baseline characteristics
| Characteristic | Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks | Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks | Total |
|---|---|---|---|
| AbbVie HCV Parent Study M13-594 (NCT02640157) | 0 Participants | 9 Participants | 9 Participants |
| AbbVie HCV Parent Study M13-596 (NCT02692703) | 0 Participants | 1 Participants | 1 Participants |
| AbbVie HCV Parent Study M14-172 (NCT02642432) | 0 Participants | 1 Participants | 1 Participants |
| AbbVie HCV Parent Study M14-242 (NCT02493855) | 1 Participants | 0 Participants | 1 Participants |
| AbbVie HCV Parent Study M14-868 (NCT02243293) | 2 Participants | 6 Participants | 8 Participants |
| AbbVie HCV Parent Study M15-410 (NCT02446717) | 0 Participants | 6 Participants | 6 Participants |
| AbbVie HCV Parent Study M15-592 (NCT03222583) | 2 Participants | 3 Participants | 5 Participants |
| AbbVie HCV Parent Study M16-126 (NCT02966795) | 0 Participants | 1 Participants | 1 Participants |
| AbbVie HCV Parent Study M16-135 (NCT03089944) | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 59.6 years STANDARD_DEVIATION 8.08 | 54.3 years STANDARD_DEVIATION 9.35 | 55.1 years STANDARD_DEVIATION 9.25 |
| Age, Customized < 65 years | 3 Participants | 23 Participants | 26 Participants |
| Age, Customized ≥ 65 years | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 26 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 1 | 1 Participants | 7 Participants | 8 Participants |
| HCV Genotype Genotype 2 | 4 Participants | 0 Participants | 4 Participants |
| HCV Genotype Genotype 3 | 0 Participants | 19 Participants | 19 Participants |
| HCV Genotype Genotype 4 | 0 Participants | 1 Participants | 1 Participants |
| HCV Genotype Genotype 5 | 0 Participants | 0 Participants | 0 Participants |
| HCV Genotype Genotype 6 | 0 Participants | 1 Participants | 1 Participants |
| HCV Ribonucleic Acid (RNA) Level | 6.79 log10 IU/mL STANDARD_DEVIATION 0.217 | 6.23 log10 IU/mL STANDARD_DEVIATION 0.958 | 6.32 log10 IU/mL STANDARD_DEVIATION 0.907 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 22 Participants | 25 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 24 Participants | 28 Participants |
| Treatment Regimen Received in AbbVie HCV Parent Study GLE/PIB | 4 Participants | 28 Participants | 32 Participants |
| Treatment Regimen Received in AbbVie HCV Parent Study OBV/PTV/RTV + DSV + RBV | 1 Participants | 0 Participants | 1 Participants |
| Treatment Response for AbbVie HCV Parent Study Breakthrough | 0 Participants | 0 Participants | 0 Participants |
| Treatment Response for AbbVie HCV Parent Study On-treatment non-responder | 0 Participants | 10 Participants | 10 Participants |
| Treatment Response for AbbVie HCV Parent Study Post-treatment relapse | 5 Participants | 18 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 28 | 0 / 33 |
| other Total, other adverse events | 5 / 5 | 21 / 28 | 26 / 33 |
| serious Total, serious adverse events | 1 / 5 | 2 / 28 | 3 / 33 |
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; 15 IU/mL) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen.
Population: Intention-to-treat (ITT) population, which included all participants who received at least 1 dose of study drug. A backward imputation method was used to impute missing responses. Participants with missing data after backward imputation were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 96.4 percentage of participants |
| Total | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 97.0 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as meeting one of the following: * confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir) at any time point during the treatment period; or * confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA \< 15 IU/mL during the treatment period, or * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment.
Time frame: 12 or 16 weeks depending on the treatment regimen
Population: Intention-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Total | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< 15 IU/mL at the end of treatment, and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.
Time frame: From the end of treatment (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen).
Population: Intention-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks | Percentage of Participants With Post-treatment Relapse | 3.6 percentage of participants |
| Total | Percentage of Participants With Post-treatment Relapse | 3.0 percentage of participants |