A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs in Adults With Hepatitis C Virus Infection, Who Are Either Treatment-naive or Treatment-experienced in Brazil

An Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin (RBV) in Treatment-Naïve or Treatment-Experienced Adults in Brazil With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (TOPAZ III)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Infection
• Intervention / Treatment: Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: ribavirin

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3-DAA ± RBV; 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg 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.	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet; Other Names: Viekira Pak; paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; dasabuvir also known as ABT-333; Drug: ribavirin; Tablet

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)	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.	12 weeks after the last actual dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks after the last actual dose of study drug
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.	12 weeks after the last actual dose of study drug
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.	12 weeks after the last actual dose of study drug
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.	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug
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	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug
(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.	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2015
• Primary Completion (Actual): July 4, 2016
• Study Completion (Actual): September 26, 2016

Study Registration Dates

• First Submitted: May 11, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Hepatitis C; Hepatitis C Genotype 1; Hepatitis C Treatment Naive; Hepatitis C Treatment Experienced; Hepatitis C Virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Ritonavir
• Other Study ID Numbers: M14-225

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No