A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (TOPAZ-II)

An Open-Label, Multicenter Study to Evaluate Long-term Outcomes With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (TOPAZ-II)

The purpose of this study was to evaluate the effect of treatment with ABT-450 co-formulated with ritonavir and ABT-267 (ABT-450/r/ABT-267) and ABT-333; 3-DAA regimen, with or without ribavirin (RBV) in adults with chronic hepatitis C virus genotype 1 (HCV GT1) infection.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Virus (HCV) Infection Genotype 1
• Intervention / Treatment: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

Detailed Description

This study (TOPAZ-II; M14-222), was a Phase 3b, open-label, multicenter study conducted in the United States which, together with its companion study TOPAZ-I (M14-423; NCT02219490) conducted outside of the United States, was designed with the primary objective of assessing the effect of treatment response on long-term clinical outcomes in adults with chronic HCV GT1 infection with or without compensated cirrhosis, who were either treatment-naïve or interferon/ribavirin (IFN/RBV) treatment- experienced. In both studies, participants were treated with the 3-DAA regimen with or without RBV. This study consisted of a screening period of up to 42 days, a treatment period of either 12 weeks for HCV GT1a-infected subjects without cirrhosis and for HCV GT1b-infected subjects without cirrhosis or with compensated cirrhosis or 24 weeks for GT1a-infected participants with compensated cirrhosis, and a 260-week post-treatment period.

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Josephs Hospital and Med Center /ID# 127800
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta, Md /Id# 126569
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group /ID# 126577
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center /ID# 128681
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Univ of Colorado Cancer Center /ID# 126568
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Health Research Institute /ID# 128683
  • Florida
    • Bradenton, Florida, United States, 34209
      • Bach and Godofsky Infec Dis /ID# 128685
    • Gainesville, Florida, United States, 32610
      • University of Florida - Archer /ID# 127787
    • Jacksonville, Florida, United States, 32256
      • Encore Borland-Groover Clinical Research /Id# 127781
    • Miami, Florida, United States, 33136
      • University of Miami /ID# 127622
    • Wellington, Florida, United States, 33414
      • South Florida Ctr Gastro, P.A. /ID# 126567
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastro Assoc /ID# 126571
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 128684
    • Chicago, Illinois, United States, 60637-1443
      • The University of Chicago Medical Center /ID# 126576
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Duplicate_Indiana University Health /ID# 126573
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2699
      • Tulane University /ID# 127779
    • Shreveport, Louisiana, United States, 71105-6800
      • Louisana Research Center, LLC /ID# 126561
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University /ID# 127791
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates - Catonsville /ID# 127624
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 126560
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System /ID# 127783
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology PA /ID# 126579
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University /ID# 126564
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
      • AGA Clinical Research Associates, LLC /ID# 126578
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey School of Medicine /ID# 128686
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102-4517
      • University of New Mexico /ID# 128859
    • Santa Fe, New Mexico, United States, 87505
      • Southwest Care Center /ID# 127784
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore University Hospital /ID# 126565
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital /ID# 128682
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 126566
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 127621
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group - GI Division /ID# 127793
    • Rochester, New York, United States, 14642
      • Univ Rochester Med Ctr /ID# 127655
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health Carolinas Medical Center /ID# 127632
    • Statesville, North Carolina, United States, 28677
      • Carolinas Center For Liver Dis /ID# 127788
  • Ohio
    • Cincinnati, Ohio, United States, 45267-2827
      • University of Cincinnati Physicians Company, LLC /ID# 127790
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC /ID# 127630
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology /ID# 127789
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One /ID# 127792
  • Texas
    • Baytown, Texas, United States, 77521-2415
      • Inquest Clinical Research /ID# 126574
    • Houston, Texas, United States, 77004
      • Cure C Consortium /ID# 126570
    • Houston, Texas, United States, 77030-2783
      • Liver Associates of Texas, P.A /ID# 126563
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research /ID# 126562
    • San Antonio, Texas, United States, 78215
      • TX Liver Inst, Americ Res Corp /ID# 127623
  • Utah
    • Murray, Utah, United States, 84123
      • Clinical Research Ctrs America /ID# 127780
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason - Seattle Orthapedics /ID# 130288
    • Seattle, Washington, United States, 98109
      • University of Washington /ID# 127785
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • Dean Clinic /ID# 126575

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control
2. Chronic hepatitis C, genotype 1-infection (HCV RNA level greater than 1,000 IU/mL at screening)
3. HCV genotype 1 infection per screening laboratory result

Exclusion Criteria:

1. Use of contraindicated medications within 2 weeks of dosing
2. Abnormal laboratory tests
3. Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus Antibody
4. History of solid organ transplant, clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation
5. Presence of hepatocellular carcinoma at screening

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: ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV); Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.

Drug: ABT-450/r/ABT-267; Tablet for oral use; Other Names: ABT-267 also known as ombitasvir; ABT-450 also known as paritaprevir; Paritaprevir/ritonavir/ombitasvir also known as Viekirax; Drug: ABT-333; Tablet for oral use; Other Names: ABT-333 also known as dasabuvir; ABT-333 also known as Exviera; Drug: Ribavirin (RBV); Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing < 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause Death: Time to Event	Time to all-cause death was defined as the number of days from the first day of study drug dosing for the participant to the date of death. All deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not die, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of all-cause death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).	At Post-Treatment Weeks 52, 104, 156, 208, and 260
Liver-Related Death: Time to Event	Time to liver-related death was defined as number of days from the 1st day of study drug dosing for the participant to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver-related death. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver-related death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).	At Post-Treatment Weeks 52, 104, 156, 208, and 260
Liver Decompensation: Time to Event	Time to liver decompensation was defined as number of days from the 1st day of study drug dosing for the participant to the date of liver decompensation. All liver decompensation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver decompensation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver decompensation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).	At Post-Treatment Weeks 52, 104, 156, 208, and 260
Liver Transplantation: Time to Event	Time to liver transplantation was defined as number of days from the 1st day of study drug dosing for the participant to date of liver transplantation. All liver transplantation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver transplantation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver transplantation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).	At Post-Treatment Weeks 52, 104, 156, 208, and 260
Hepatocellular Carcinoma: Time to Event	Time to hepatocellular carcinoma was defined as number of days from the 1st day of study drug dosing for the participant to date of hepatocellular carcinoma. All hepatocellular carcinoma was to be included, whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For those with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for hepatocellular carcinoma. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of hepatocellular carcinoma included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).	At Post-Treatment Weeks 52, 104, 156, 208, and 260
All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event	Time to the composite of clinical outcomes is the time to the first occurrence of all-cause death, liver-related death, liver decompensation, liver transplantation, or hepatocellular carcinoma. All first occurrences were to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not experience any of these events, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. Pre-specified analysis included pooled data from this study and from TOPAZ-I; NCT02219490.	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	12 weeks after the last actual dose of study drug
Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Physical Component Summary (PCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument 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 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Mental Component Summary (MCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument 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 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Post-Treatment Week 12 and Post-Treatment Week 24	The FACIT-F is a symptom specific instrument with a focus on measuring fatigue in a variety of chronic diseases or health conditions. It was originally developed from interviews with oncology patients and clinical experts to assess anemia-associated fatigue. Its 13-item-version assesses peripheral, central, or mixed fatigue with a recall period of 7 days and yields a summed total score ranging between 0 and 52. Higher FACIT-F scores indicate a lesser degree of fatigue. Positive numbers indicate improvement from baseline.	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets	Treatment compliance was calculated as the percentage of tablets taken (presumed as [tablets dispensed-tablets returned]) relative to the total tablets, respectively, expected to be taken. Study drug interruptions due to an adverse event or other planned interruptions recorded on the electronic case report form (eCRF) were to be subtracted from the duration. For compliance to ribavirin (RBV), RBV dose modifications due to adverse events, toxicity management, or weight changes as recorded on the RBV Dose Modifications eCRF were to be used to modify the total number of tablets that should have been taken. A participant is considered to be compliant if the percentage is between 80% and 120%.	Up to Treatment Week 24

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2014
• Primary Completion (Actual): May 13, 2021
• Study Completion (Actual): May 13, 2021

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: June 18, 2014
• First Posted (Estimate): June 19, 2014

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Cirrhosis; Compensated Cirrhosis; Hepatitis C Genotype 1; Hepatitis C; Hepatitis C Virus; Naïve; Relapser; Treatment-Experienced; Non responder; Null responder
• 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: M14-222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

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