Coadministration of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) With Ribavirin (RBV) in Adults With Genotype 4 (GT4) Hepatitis C Virus (HCV) in Egypt

An Open-Label Study to Evaluate the Safety and Efficacy of the Coadministration of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) With Ribavirin (RBV) in Adults With Chronic Hepatitis C Virus Genotype 4 Infection in Egypt

This study evaluates the efficacy and safety of ABT-450/r/ABT-267 with RBV in treatment-naive and treatment-experienced HCV GT4 subjects without or with compensated cirrhosis.

Study Overview

• Status: Completed
• Conditions: HCV; Hepatitis C Infection; Genotype 4
• Intervention / Treatment: Drug: 2 DAA; Drug: RBV

Detailed Description

Non-cirrhotic subjects were directly enrolled into Arm A. Cirrhotic subjects were randomized to either Arm B (12 weeks of treatment) or Arm C (24 weeks of treatment).

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hepatitis C, genotype 4-infection (hepatitis C virus [HCV] ribonucleic acid [RNA] level greater than 1,000 IU/mL at Screening)

• Subjects must meet one of the following:

  • Treatment-naive: Subject has never received antiviral treatment for HCV infection OR
  • Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegylated-interferon [pegIFN]/RBV);
• Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control
• In substudy 1, demonstrated absence of liver cirrhosis as confirmed by liver biopsy or Fibroscan
• In substudy 2, evidence of liver cirrhosis as confirmed by liver biopsy or Fibroscan with Child-Pugh score less than or equal to 6 at Screening and confirmed absence of hepatocellular carcinoma

Exclusion Criteria:

• Females who are pregnant or breastfeeding
• Positive screen for hepatitis B Surface antigen or anti-Human Immunodeficiency virus antibody
• HCV genotype performed during screening indicating unable to genotype or co-infection with any other HCV genotype
• abnormal laboratory tests
• self-reports current drinking more than 2 drinks per day
• current enrollment in another investigational study
• previous treatment with a direct acting antiviral agent (DAA) containing regimen
• In substudy 1, evidence of liver cirrhosis
• In substudy 2, evidence of current or past Child-Pugh B or C classification and confirmed presence of hepatocellular carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; ABT-450/r/ABT-267 (paritaprevir/ritonavir/ombitasvir; 2 direct acting antiviral agent [DAA]) plus Ribavirin (RBV) for 12 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants without cirrhosis.	Drug: 2 DAA; ABT-450/r/ABT-267 tablets; Drug: RBV; Ribavirin tablets
Active Comparator: Arm B; ABT-450/r/ABT-267 plus RBV for 12 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants with compensated cirrhosis.	Drug: 2 DAA; ABT-450/r/ABT-267 tablets; Drug: RBV; Ribavirin tablets
Active Comparator: Arm C; ABT-450/r/ABT-267 plus RBV for 24 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants with compensated cirrhosis.	Drug: 2 DAA; ABT-450/r/ABT-267 tablets; Drug: RBV; Ribavirin tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm	SVR12 was defined as 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.	12 weeks after last dose
Number of Participants With Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.	Screening until 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm	On-treatment virologic failure was defined as quantifiable HCV RNA throughout the entire treatment period with at least 6 weeks of treatment, confirmed HCV RNA greater than the LLOQ after previously having unquantifiable HCV RNA, or a confirmed increase from nadir of at least one log10 in HCV RNA during treatment.	Up to 12 or 24 weeks after first dose
Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm	Post-treatment relapse was defined as 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 < LLOQ at the end of treatment.	Up to 12 weeks after first dose

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Sarah Kopecky-Bromberg, PhD, AbbVie

Publications and helpful links

General Publications

• Waked I, Shiha G, Qaqish RB, Esmat G, Yosry A, Hassany M, Soliman R, Mohey MA, Allam N, Zayed N, Asselah T, Hall C, Redman R, Mobashery N, Doss W. Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial. Lancet Gastroenterol Hepatol. 2016 Sep;1(1):36-44. doi: 10.1016/S2468-1253(16)30002-4. Epub 2016 Jun 16. Erratum In: Lancet Gastroenterol Hepatol. 2016 Sep;1(1):e1.

Study record dates

Study Major Dates

• Study Start: November 4, 2014
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: September 19, 2014
• First Submitted That Met QC Criteria: September 22, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: HCV; Cirrhosis; treatment experienced; Egypt; Genotype 4; non-responder; naive; hepatitis c; compensated cirrhosis; null responder; partial responder; relapser; hepatitis infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: M14-250