Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study
- Conditions
- Hepatitis C Virus Infection
- Interventions
- Registration Number
- NCT02939989
- Lead Sponsor
- AbbVie
- 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)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks Glecaprevir/Pibrentasvir Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor (PI) and/or nonstructural viral protein 5A inhibitor (NS5Ai) prior to participation in AbbVie HCV parent study received daily treatment with glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg plus sofosbuvir (SOF) 400 mg plus twice-daily weight-based ribavirin (RBV) 600 mg - 1200 mg daily total for 12 weeks. Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks Glecaprevir/Pibrentasvir 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. Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks Sofosbuvir Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor (PI) and/or nonstructural viral protein 5A inhibitor (NS5Ai) prior to participation in AbbVie HCV parent study received daily treatment with glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg plus sofosbuvir (SOF) 400 mg plus twice-daily weight-based ribavirin (RBV) 600 mg - 1200 mg daily total for 12 weeks. Glecaprevir/Pibrentasvir + SOF + RBV for 12 weeks Ribavirin Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor (PI) and/or nonstructural viral protein 5A inhibitor (NS5Ai) prior to participation in AbbVie HCV parent study received daily treatment with glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg plus sofosbuvir (SOF) 400 mg plus twice-daily weight-based ribavirin (RBV) 600 mg - 1200 mg daily total for 12 weeks. Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks Sofosbuvir 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. Glecaprevir/Pibrentasvir + SOF + RBV for 16 weeks Ribavirin 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
Trial Locations
- Locations (26)
Ruane Clinical Research Group /ID# 155714
🇺🇸Los Angeles, California, United States
Beijing Di Tan Hospital, Capital Medical University /ID# 218496
🇨🇳Beijing, China
University of Calgary /ID# 155726
🇨🇦Calgary, Alberta, Canada
Auckland City Hospital /ID# 200945
🇳🇿Grafton, Auckland, New Zealand
University of Buffalo /ID# 155721
🇺🇸Buffalo, New York, United States
Medical Company Hepatolog /ID# 214314
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Dunedin Hospital /ID# 155591
🇳🇿Otago, New Zealand
Asklepios Klinik St. Georg /ID# 155733
🇩🇪Hamburg, Germany
Hospital Universitario Puerta de Hierro, Majadahonda /ID# 155734
🇪🇸Majadahonda, Madrid, Spain
Zentru fur HIV und Heaptogastroenterologie /ID# 155592
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Mengchao Hepatobiliary Hospital of Fujian Medical University /ID# 218495
🇨🇳Fuzhou, China
Inselspital, Universitätsspital Bern /ID# 155716
🇨🇭Bern, Switzerland
Duplicate_Imperial College Healthcare NHS Trust /ID# 155718
🇬🇧London, United Kingdom
Digestive Health Specialists of the Southeast /ID# 155719
🇺🇸Dothan, Alabama, United States
Digestive Disease Associates - Baltimore /ID# 155713
🇺🇸Baltimore, Maryland, United States
Henry Ford Health System /ID# 155720
🇺🇸Detroit, Michigan, United States
The Royal Melbourne Hospital /ID# 155727
🇦🇺Parkville, Victoria, Australia
West China Hospital, Sichuan University /ID# 217613
🇨🇳Chengdu, China
The First Hospital Affiliated to AMU (Southwest Hospital) /ID# 218494
🇨🇳Chongqing, China
Samsung Medical Center /ID# 214844
🇰🇷Seoul, Korea, Republic of
Waikato Hospital /ID# 155728
🇳🇿Hamilton, Waikato, New Zealand
Duplicate_Karolinska Univ Sjukhuset /ID# 155735
🇸🇪Solna, Sweden
Carolinas Center For Liver Dis /ID# 155731
🇺🇸Statesville, North Carolina, United States
Gastro One /ID# 155729
🇺🇸Germantown, Tennessee, United States
TX Liver Inst, Americ Res Corp /ID# 157881
🇺🇸San Antonio, Texas, United States
Royal Brisbane and Women's Hospital /ID# 200944
🇦🇺Herston, Queensland, Australia