A Study to Evaluate Chronic Hepatitis C Infection in Adult Transplant Recipients

Phase 2

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: ombitasvir/paritaprevir/ritonavir; Drug: ribavirin

• Registration Number: NCT01782495
• Lead Sponsor: AbbVie

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ABT-450/r/ABT-267 with or without ABT-333 and with or without ribavirin (RBV) in adult liver or renal transplant recipients with hepatitis C virus (HCV) genotype 1 or 4 (GT1 or GT4) infection.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-01-22
• Study First Submitted QC: 2013-01-31
• Study First Posted: 2013-02-04
• Study Start: 2013-02-25
• Primary Completion: 2016-11-02
• Study Completion: 2017-07-13
• Status Verified: 2017-10
• Results First Submitted: 2017-10-09
• Results First Submitted QC: 2017-10-09
• Last Update Submitted: 2017-10-09
• Results First Posted: 2017-11-07
• Last Update Posted: 2017-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 129

Inclusion Criteria

• Male or female, at least 18 years of age at the time of screening.
• Currently taking an immunosuppressant regimen based on either tacrolimus or cyclosporine. Corticosteroids such as prednisone or prednisolone are permitted as components of the immunosuppressant regimen providing the dose is not more than 10 mg/day.
• Hepatitis C virus (HCV) interferon (IFN) therapy treatment-naïve or -experienced, either pre- or post-liver or renal transplant.
• Screening HCV genotype testing indicating infection with genotype 1 or 4 (GT1 or GT4) only.

Exclusion Criteria

• Use of everolimus or sirolimus as part of the immunosuppressive regimen within 2 months of Screening Visit.
• Use of any medications contraindicated for use with the study regimen as well as those that are contraindicated for use with either ritonavir or ribavirin within 2 weeks prior to study drugs administration or 10 half-lives (if known), whichever is longer.
• Positive test result for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab).
• Documented history of post-transplant complications directly involving the hepatic or renal vasculature as appropriate to the organ transplanted, e.g., thrombosis of the portal vein, the hepatic artery and/or hepatic vein.
• Clinically significant abnormalities, other than HCV infection, in a subject post-transplant based upon the medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) that make the subject an unsuitable candidate for this study in the opinion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm C	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant receipts with HCV genotype 1b infection who were treatment naïve or prior responders to interferon treatment without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 24 weeks.
Arm D	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1a infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (dosed 1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm I	ombitasvir/paritaprevir/ritonavir and dasabuvir	Renal transplant recipients with HCV genotype 1b infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 12 weeks.
Arm F	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm G	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1b infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 12 weeks.
Arm E	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1b infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm H	ombitasvir/paritaprevir/ritonavir and dasabuvir	Renal transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm H	ribavirin	Renal transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm B	ombitasvir/paritaprevir/ritonavir and dasabuvir	Liver transplant recipients with HCV genotype 1a or genotype 1b (dependent on prior treatment experience and response) infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm A	ribavirin	Liver transplant recipients with HCV genotype 1 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm B	ribavirin	Liver transplant recipients with HCV genotype 1a or genotype 1b (dependent on prior treatment experience and response) infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm D	ribavirin	Liver transplant recipients with HCV genotype 1a infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (dosed 1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm E	ribavirin	Liver transplant recipients with HCV genotype 1b infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm F	ribavirin	Liver transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm J	ombitasvir/paritaprevir/ritonavir	Liver transplant recipients with HCV genotype 4 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm J	ribavirin	Liver transplant recipients with HCV genotype 4 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks.
Arm K	ombitasvir/paritaprevir/ritonavir	Liver transplant recipients with HCV genotype 4 infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks.
Arm K	ribavirin	Liver transplant recipients with HCV genotype 4 infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 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	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 after backward imputation were imputed as nonresponders.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24)	24 weeks after the last actual dose of study drug	SVR24 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 24 weeks after the last dose of study drug. Participants with missing data after backward imputation were imputed as nonresponders.
Percentage of Participants With On-treatment Virologic Failure	Up to 12 weeks (for 12-week treatment) or 24 weeks (for 24-week treatment)	On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment, or confirmed HCV RNA ≥ LLOQ at any point during treatment after HCV RNA \< LLOQ, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment.
Percentage of Participants With Post-treatment Relapse	From the end of treatment through 12 weeks after the last dose of study drug	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment.