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

Phase 3CompletedNCT02219490

AbbVie1,596 enrolled

Overview

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.

This study (TOPAZ-I; M14-423), was a Phase 3b, open-label, multicenter study conducted outside of the United States which, together with its companion study TOPAZ-II (M14-222; NCT 02167945) conducted in 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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

1,596

Conditions

Chronic Hepatitis C Virus (HCV) Infection Genotype 1

Interventions

ABT-450/r/ABT-267DRUG

Tablet for oral use

ABT-333DRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Males and females at least 18 years old at screening 2. Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control 3. Chronic hepatitis C, genotype 1 infection 4. Males must be surgically sterile or agree to practice acceptable forms of birth control 5. Screening laboratory result indicating HCV genotype 1 infection Exclusion Criteria: 1. Use of contraindicated medications within 2 weeks of dosing 2. Abnormal laboratory tests 3. Current or past clinical evidence of Child-Pugh B or C classification or history of liver decompensation 4. Confirmed presence of hepatocellular carcinoma 5. History of solid organ transplant

Locations (187)

Outcomes

Primary Outcomes

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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260

Liver-Related Death: Time to Event

Time to liver-related death was defined as days from the 1st day of study drug dosing for the subject to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while subject was still taking study drug or had previously discontinued study drug. If the subject didn't experience event of interest nor had died (all-cause death), their data was to be censored at date of last available assessment. For those with no post-baseline assessment, data was to be censored on 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).

Time frame: 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).

Data from ClinicalTrials.gov

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CHU Bab El Oued /ID# 145420

Algiers, Algeria

CHU Bologhine Hospital /ID# 145421

Algiers, Algeria

CHU Mustapha Bacha /ID# 132130

Algiers, Algeria

St Vincent's Hospital Sydney /ID# 131001

Darlinghurst, New South Wales, Australia

Nepean Hospital /ID# 130999

Kingswood, New South Wales, Australia

Westmead Hospital /ID# 130997

Westmead, New South Wales, Australia

Greenslopes Private Hospital /ID# 131003

Greenslopes, Queensland, Australia

Royal Brisbane and Women's Hospital /ID# 131004

Herston, Queensland, Australia

Royal Adelaide Hospital /ID# 131002

Adelaide, South Australia, Australia

St Vincent's Hospital Melbourne /ID# 131000

Fitzroy Melbourne, Victoria, Australia

...and 177 more locations

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260

Liver Transplantation: Time to Event

Time to liver transplantation was defined as days from 1st day of study drug dosing for subject to date of liver transplantation. All liver transplantation was to be included, whether it occurred while the subject was still taking study drug or had previously discontinued study drug. If the subject didn't experience event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment. For those with no post-baseline assessment, data was to be censored on 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260

Hepatocellular Carcinoma: Time to Event

Time to hepatocellular carcinoma (HCC) was defined as number of days from 1st day of study drug dosing for subject to date of hepatocellular carcinoma. All HCC was to be included, whether it occurred while subject was still taking study drug or had previously discontinued study drug. If the subject 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. 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 HCC. 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).

Time frame: 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-II; NCT02167945.

Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260

Secondary Outcomes

Change From Baseline in FibroScan Score by SVR12 Status

The FibroScan test is a validated non-invasive test used to assess liver fibrosis in participants with chronic liver disease, and it was performed at study sites where it was available. For participants with Hepatitis C infection, a FibroScan score of 2-7 kPa indicates no liver scarring or mild scarring; a score of 8 or 9 is associated with moderate liver scarring; 9-14 indicates severe liver scarring; and 14 or higher is indicative of advanced liver scarring, cirrhosis. Negative changes from baseline indicate improvement in liver fibrosis.

Time frame: At the final treatment visit and Post-Treatment Weeks 12, 24, 52, 104, 156, 208, and 260

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. Flanking imputation, where applicable, was used to impute missing data. After applying flanking imputation, if there was no value in the window but there was an HCV RNA value from a local laboratory present, then it was to be imputed into the SVR window. Otherwise, participants with missing data were counted as failures.

Time frame: 12 weeks after the last actual dose of study drug