Chronic Hepatitis C Virus (HCV) Infection Genotype 1Phase 3TOPAZ-IINCT02167945

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

A Phase 3 study testing ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV) in people with Chronic Hepatitis C Virus (HCV) Infection Genotype 1, run by AbbVie at 48 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Chronic Hepatitis C Virus (HCV) Infection Genotype 1
What is being tested?: ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 615 participants
Where: 48 sitesUnited States
Study dates: 12 Jun 2014to 13 May 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

48 sites in 1 country.

City, postcode or hospital

48 sites in 1 country

United States48 sites

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

Other trials in United States

About this study

Official title: 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)

Read the 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.

Conditions: Chronic Hepatitis C Virus (HCV) Infection Genotype 1
Being tested: ABT-450/r/ABT-267, ABT-333, Ribavirin (RBV)
Keywords: Hepatitis C Genotype 1, Compensated Cirrhosis, Cirrhosis, Naïve, Hepatitis C, Hepatitis C Virus, Treatment-Experienced, Relapser, Null responder, Non responder
Medical subject headings: Hepatitis C, Chronic, Hepatitis C, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ABT-450/r/ABT-267Drug
Also called ABT-450 also known as paritaprevir, ABT-267 also known as ombitasvir, Paritaprevir/ritonavir/ombitasvir also known as Viekirax
Tablet for oral use
ABT-333Drug
Also called ABT-333 also known as dasabuvir, ABT-333 also known as Exviera
Tablet for oral use
Ribavirin (RBV)Drug
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.

Study groups in NCT02167945
Study group	Role	What they receive
ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)	Experimental	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. Receives: Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: At Post-Treatment Weeks 52, 104, 156, 208, and 260

Secondary outcomes (5)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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%.
Measured: Up to Treatment Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Jun 201413 May 2021

First posted19 Jun 2014 (estimated)
Study start12 Jun 2014
Primary completion13 May 2021
Study completion13 May 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Hepatitis C Virus (HCV) Infection Genotype 1Studies of the same condition, open and under way.
More trials run by AbbVieThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 615 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02167945
Sponsor's protocol ID: M14-222
Acronym: TOPAZ-II
Status last verified: Jun 2022
First submitted: 18 Jun 2014
Last updated: 19 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Study at a glance

From the registry record, last updated by the sponsor on 19 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT02167945
Acronym / sponsor ID: TOPAZ-II / M14-222
Conditions: Chronic Hepatitis C Virus (HCV) Infection Genotype 1
Keywords: Hepatitis C Genotype 1, Compensated Cirrhosis, Cirrhosis, Naïve, Hepatitis C, Hepatitis C Virus, Treatment-Experienced, Relapser
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 615 participants (actual)
Lead sponsor: AbbVieIndustry (pharma, biotech, devices)
Study start: 12 Jun 2014 (actual)
Primary completion: 13 May 2021 (actual)
Study completion: 13 May 2021 (actual)
First posted: 19 Jun 2014 (estimated)
Results: Posted 6 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)	Experimental	Drug: ABT-450/r/ABT-267, Drug: ABT-333, Drug: 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.

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ABT-450/r/ABT-267Also: ABT-450 also known as paritaprevir, ABT-267 also known as ombitasvir, Paritaprevir/ritonavir/ombitasvir also known as ViekiraxTablet for oral use	Drug	ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)
ABT-333Also: ABT-333 also known as dasabuvir, ABT-333 also known as ExvieraTablet for oral use	Drug	ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)
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.	Drug	ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

Primary outcome

All-Cause Death: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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).
Liver-Related Death: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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).
Liver Decompensation: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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).
Liver Transplantation: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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).
Hepatocellular Carcinoma: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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).
All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
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.

5 secondary outcomes

Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets
Time frame: Up to Treatment Week 24

Results and safety

Results posted to the registry on 6 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)	615	366

Primary outcome: All-Cause Death: Time to Event

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 n = 77	Participants in Studies M14-222 and M14-423 Who Achieved SVR12 n = 2134
Kaplan-Meier estimate at PT Week 52	8.3 (3.1 to 21.2)	0.1 (0.1 to 0.4)
Kaplan-Meier estimate at PT Week 104	8.3 (3.1 to 21.2)	0.7 (0.4 to 1.1)
Kaplan-Meier estimate at PT Week 156	8.3 (3.1 to 21.2)	1.2 (0.8 to 1.8)
Kaplan-Meier estimate at PT Week 208	8.3 (3.1 to 21.2)	1.5 (1.1 to 2.2)
Kaplan-Meier estimate at PT Week 260	8.3 (3.1 to 21.2)	2.0 (1.5 to 2.8)

Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: p <0.001, Log-rank test
Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: Cox Proportional Hazard Ratio: 0.126 (95% CI 0.044 to 0.358), p <0.001, Cox proportional hazards model

Population analysed: Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Primary outcome: Liver-Related Death: Time to Event

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 n = 77	Participants in Studies M14-222 and M14-423 Who Achieved SVR12 n = 2134
Kaplan-Meier estimate at PT Week 52	1.4 (0.2 to 9.6)	0 (NA to NA)
Kaplan-Meier estimate at PT Week 104	1.4 (0.2 to 9.6)	0 (NA to NA)
Kaplan-Meier estimate at PT Week 156	1.4 (0.2 to 9.6)	0.1 (0.1 to 0.4)
Kaplan-Meier estimate at PT Week 208	1.4 (0.2 to 9.6)	0.1 (0.1 to 0.4)
Kaplan-Meier estimate at PT Week 260	1.4 (0.2 to 9.6)	0.1 (0.1 to 0.4)

Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: p <0.001, Log-rank test
Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: Cox Proportional Hazard Ratio: 0.031 (95% CI 0.003 to 0.380), p = 0.007, Cox proportional hazards model

Primary outcome: Liver Decompensation: Time to Event

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 n = 77	Participants in Studies M14-222 and M14-423 Who Achieved SVR12 n = 2134
Kaplan-Meier estimate at PT Week 52	4.5 (1.5 to 13.4)	0.2 (0.1 to 0.5)
Kaplan-Meier estimate at PT Week 104	4.5 (1.5 to 13.4)	0.2 (0.1 to 0.5)
Kaplan-Meier estimate at PT Week 156	4.5 (1.5 to 13.4)	0.3 (0.1 to 0.6)
Kaplan-Meier estimate at PT Week 208	4.5 (1.5 to 13.4)	0.3 (0.2 to 0.7)
Kaplan-Meier estimate at PT Week 260	4.5 (1.5 to 13.4)	0.5 (0.2 to 0.9)

Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: p <0.001, Log-rank test
Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: Cox Proportional Hazard Ratio: 0.038 (95% CI 0.009 to 0.156), p <0.001, Cox proportional hazards model

Primary outcome: Liver Transplantation: Time to Event

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 n = 77	Participants in Studies M14-222 and M14-423 Who Achieved SVR12 n = 2134
Kaplan-Meier estimate at PT Week 52	0 (NA to NA)	0 (NA to NA)
Kaplan-Meier estimate at PT Week 104	0 (NA to NA)	0 (NA to NA)
Kaplan-Meier estimate at PT Week 156	0 (NA to NA)	0.1 (0.1 to 0.4)
Kaplan-Meier estimate at PT Week 208	0 (NA to NA)	0.1 (0.1 to 0.4)
Kaplan-Meier estimate at PT Week 260	0 (NA to NA)	0.2 (0.1 to 0.5)

Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: p = 0.860, Log-rank test
Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 vs Participants in Studies M14-222 and M14-423 Who Achieved SVR12: p = 0.997, Cox proportional hazards model

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality is reported from enrollment to the end of study, up to five years of follow-up. Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after the last study drug administration, up to 213 days. After Post-Treatment Week 4 until the end of the study, only SAE of death was to be collected.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)	25 of 615 (4.1%)	381 of 615 (62%)	19 of 615

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

ABBVIE INC. study director

AbbVie

48 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ABT-450/r/ABT-267, ABT-333 and Ribavirin (RBV) in people with Chronic Hepatitis C Virus (HCV) Infection Genotype 1, run by AbbVie at 48 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-Cause Death: Time to Event (time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02167945.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2022.