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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-I)

Primary Purpose

Chronic Hepatitis C Virus (HCV) Infection Genotype 1

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

ABT-450/r/ABT-267

ABT-333

Ribavirin (RBV)

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Virus (HCV) Infection Genotype 1 focused on measuring Hepatitis C Genotype 1, Compensated Cirrhosis, Cirrhosis, Naive, Hepatitis C, Hepatitis C Virus, Treatment-Experienced, Relapser, Null responder, Non responder

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Males and females at least 18 years old at screening
Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control
Chronic hepatitis C, genotype 1 infection
Males must be surgically sterile or agree to practice acceptable forms of birth control
Screening laboratory result indicating HCV genotype 1 infection

Exclusion Criteria:

Use of contraindicated medications within 2 weeks of dosing
Abnormal laboratory tests
Current or past clinical evidence of Child-Pugh B or C classification or history of liver decompensation
Confirmed presence of hepatocellular carcinoma
History of solid organ transplant

Sites / Locations

CHU Bab El Oued /ID# 145420
CHU Bologhine Hospital /ID# 145421
CHU Mustapha Bacha /ID# 132130
St Vincent's Hospital Sydney /ID# 131001
Nepean Hospital /ID# 130999
Westmead Hospital /ID# 130997
Greenslopes Private Hospital /ID# 131003
Royal Brisbane and Women's Hospital /ID# 131004
Royal Adelaide Hospital /ID# 131002
St Vincent's Hospital Melbourne /ID# 131000
The Royal Melbourne Hospital /ID# 130998
Ordensklinikum Linz GmbH Elisabethinen /ID# 131017
Medizinische Universitaet Graz /ID# 131018
Medizinische Universitaet Wien /ID# 131015
Cliniques Universitaires de Bruxelles Hopital Erasme /ID# 131020
UCL Saint-Luc /ID# 131019
Universitair Ziekenhuis Leuven /ID# 131021
Tokuda Hospital Sofia /ID# 131022
UMHAT Sveti Ivan Rilski /ID# 131026
Univ Hosp for Active Treat /ID# 131023
Diagnostic Consultative Center /ID# 131027
UMHAT Sveta Marina /ID# 131025
University of Calgary /ID# 134370
GI Research & Associates /ID# 132169
LAIR Centre /ID# 130970
Vancouver Infectious Diseases Centre /ID# 134369
GIRI Gastrointestinal Research Institute /ID# 132171
University of Manitoba / Health Scuience Centre / John Buhler Research Centre /ID# 130969
Saint John Regional Hospital /ID# 131210
Ottawa Hospital Research Institute /ID# 132170
Toronto General Hospital /ID# 132134
Toronto Liver Centre /ID# 132168
Toronto Digestive Disease Asso /ID# 130968
Clinique Medicale L'Actuel /ID# 132167
Jewish General Hospital /ID# 132165
Royal Victoria Hospital / McGill University Health Centre /ID# 132166
CHU de Quebec-Université Laval hôpital CHUL /ID# 132132
Kobenhavns Universitet - Hvidovre Hospital (HH) /ID# 131031
Odense University Hospital /ID# 131029
Aarhus Univ Hospital, Skejby /ID# 131030
Helsinki University Hospital /ID# 131034
Turku University Hospital /ID# 131032
Hopital Saint Joseph /ID# 132177
CHU Limoges - Dupuytren 1 /ID# 131038
Hopital Haut-Lévêque /ID# 131036
Hopital Saint Eloi /ID# 131037
CHU de Nantes, Hotel Dieu -HME /ID# 132179
Hopital Jean Verdier /ID# 135877
CHU Grenoble - Hopital Michallon /ID# 131041
HCL - Hopital de la Croix-Rousse /ID# 131042
Duplicate_Hopital lArchet 2 /ID# 131040
CHRU Pontchaillou /ID# 132173
CHU Strasbourg - Hopital Civil /ID# 132174
Hopital Universitaire Purpan Hopital Rangueil /ID# 131035
Universitaetsklinikum Freiburg /ID# 131044
Universitaetsklinik Heidelberg /ID# 134371
Universitaetsklinikum Tuebingen Medizinische Klinik /ID# 131045
LMU Klinikum der Universitat Muchen /ID# 131049
Universitaetsklinikum Frankfurt /ID# 131055
Zentru fur HIV und Heaptogastroenterologie /ID# 131052
Gastroenterologische Gemeinschaftspraxis Herne /ID# 131050
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie /ID# 131053
Universitaetsklinikum Essen /ID# 131048
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 131051
Medizinische Hochschule Hannover /ID# 131054
Centrum für interdisziplinaere Medizin /ID# 131046
General Hospital of Athens Ippokratio /ID# 131057
General Hospital of Athens Laiko /ID# 131088
General University Hospital of Alexandroupolis /ID# 131056
Beaumont Hospital /ID# 131089
St James Hospital /ID# 132180
St Vincent's University Hospital /ID# 132181
The Chaim Sheba Medical Center /ID# 131092
Tel Aviv Sourasky Medical Center /ID# 132182
Rambam Health Care Campus /ID# 131090
The Lady Davis Carmel Medical Center /ID# 131091
Duplicate_A.O.U. Policlinico S.Orsola-Malpighi /ID# 131095
Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant Anna /ID# 131102
Fondazione di Religione e di Culto Casa Sollievo della Sofferenza /ID# 132190
Policlinico Agostino Gemelli /ID# 131098
Ospedale San Raffaele IRCCS /ID# 131093
Fondazione PTV Policlinico Tor Vergata /ID# 132185
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 132188
Azienda Ospedaliero Universitaria Careggi /ID# 132197
Azienda Ospedaliera Universitaria Ospedali Riuniti /ID# 132195
A.O.U. Policlinico G. Martino /ID# 132193
ASST Fatebenefratelli Sacco-Ospedale Sacco /ID# 134372
Azienda Ospedaliera Niguarda Ca' Granda Hospital /ID# 131104
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 131097
Ospedale S Giuseppe /ID# 132194
ASST Santi Paolo e Carlo/Presidio Ospedale San Paolo /ID# 132198
Azienda Ospedaliera Universitaria Federico II /ID# 131096
Azienda Ospedaliera Universitaria Federico II /ID# 132191
Azienda Ospedaliera Universitaria Paolo Giaccone /ID# 132184
Azienda Ospedaliero-Universitaria di Parma /ID# 132183
Azienda Ospedaliera Universitaria "San Giovanni di Dio e Ruggi d'Aragona /ID# 132192
A.O.U. Citta della Salute e della Scienza di Torino /ID# 131100
Azienda Ospedaliera Universitaria Friuli Centrale/Presidio Ospedaliero Universit /ID# 132196
Hospital General de Tijuana /ID# 130972
Cife /Id# 130974
ITESM campus Ciudad de Mexico /ID# 132383
Instituto Metropolitano de Inv /ID# 132201
Instituto Nacional de Clencias Medicas y Nutricion Salvador Zubrian Departament /ID# 130975
CIF-BIOTEC/Medica Sur /ID# 134971
Erasmus Medisch Centrum /ID# 132206
Academisch Medisch Centrum /ID# 132205
Leids Universitair Medisch Centrum /ID# 132204
Akershus Universitetssykehus_MAIN /ID# 132212
St. Olavs Hospital HF /ID# 132213
Stavanger University Hospital /ID# 132211
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza /ID# 131106
Wojewodzki Specjalistyczny Szpital im. dr. W. Bieganskiego /ID# 131107
Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 131115
Wojewodzki Szpital Zakazny /ID# 131112
Uniwersytecki Szpital Kliniczny w Bialymstoku /ID# 131108
ID Clinic /ID# 131111
Centro Hospitalar e Universitario de Coimbra, EPE /ID# 131119
Centro Hospitalar Universitario Lisboa Central, EPE - Hospital dos Capuchos /ID# 131116
Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 131118
Centro Hospitalar Universitário do Porto, EPE - Hospital Santo António /ID# 131117
Duplicate_Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 131120
Institutul Clinic Fundeni /ID# 131121
Spitalul Clinic de Boli Infectioase Si Pneumoftiziologie Dr. Victor Babes /Id# 131126
Institutul Nat. de Boli Infectioase /ID# 131124
SC Gastromedica SRL /ID# 131127
Medical Company Hepatolog /ID# 132277
Republican Clinical Infectious Diseases Hospital n.a. Professor A. F. Agafonov /ID# 132270
South-Ural State Med. Academy /ID# 132274
Kuzbass Center for Prevention and Fight agains AIDS /ID# 132269
Krasnoyarsk Regional Center for the Prevention and Control of AIDS /ID# 132278
Moscow Clinical Scientific Center n.a. Loginov /ID# 132266
Central Clinical Hospital of Russian Academy of Science /ID# 132289
I. M. Sechenov First Moscow State Medical University /ID# 132275
City Clinical Hospital #24 /ID# 132268
Research Institute of Emergency Medicine named after V.I. N.V. Sklifosovsky /ID# 132288
Clinical Infectious Diseases Hospital #1 /ID# 132272
Samara State Medical University /ID# 136913
Stavropol State Medical University /ID# 132279
Tolyatti City Clinical Hospital #1 /ID# 132273
Multidisciplinary Consultative and Diagnostic Center /ID# 131130
Sverdlovsk Regional Clinical Hospital #1 /ID# 132267
King Abdulaziz Medical City /ID# 145129
Ministry Nat Guard Hosp Health /ID# 145126
King Khalid University Hospita /ID# 132291
Hospital Universitario Central de Asturias /ID# 131138
Hospital Universitario Germans Trias i Pujol /ID# 132293
Hospital Unversitario Marques de Valdecilla /ID# 131141
Hospital Donostia /ID# 131144
Hospital Universitari Son Espases /ID# 131140
Hospital General Universitario Santa Lucia /ID# 131139
OSI Ezkerraldea-Enkarterri-Cruces /ID# 131143
Hospital Universitario A Coruna - CHUAC /ID# 131137
Hospital Universitario Reina Sofia /ID# 131135
Hospital Universitario de la Princesa /ID# 131131
Hospital Universitario 12 de Octubre /ID# 131133
Hospital Universitario La Paz /ID# 131132
Hospital Universitario Virgen de la Victoria /ID# 131136
Hospital Universitario Virgen del Rocio /ID# 131134
Hospital Clinico Universitario Lozano Blesa /ID# 132292
Skane University hospital /ID# 131146
Karolinska University Hospital Solna /ID# 131145
Sahlgrenska University Hospital /ID# 131147
Kantonsspital St. Gallen /ID# 131148
Universitätsspital Zürich /ID# 134881
Inselspital, Universitätsspital Bern /ID# 132294
Izmir Tepecik Training and Research Hospital /ID# 134968
Hacettepe University Faculty of Medicine /ID# 131150
Ankara Univ Medical Faculty /ID# 131151
Uludag University Medical Faculty /ID# 132297
Istanbul University Istanbul Medical Faculty /ID# 131153
Ege University Medical Faculty /ID# 132298
Karadeniz University /ID# 131152
Duplicate_University Hospitals Dorset NHS Foundation Trust /ID# 132306
University Hospital Southampton NHS Foundation Trust /ID# 131161
Barts Health NHS Trust /ID# 132302
The Royal Free London NHS Foundation Trust /ID# 131159
Duplicate_Nottingham University Nottingham University Hospitals NHS Trust /ID# 131155
NHS Greater Glasgow and Clyde /ID# 131162
University Hospitals Birmingham NHS Foundation Trust /ID# 131154
Duplicate_NHS Tayside /ID# 132300
NHS Lothian /ID# 134368
Leeds Teaching Hospitals NHS Trust /ID# 132305
King's College Hospital NHS Foundation Trusts /ID# 131157
University Hospital Plymouth NHS Trust /ID# 131160
Portsmouth Hospitals University NHS Trust /ID# 131158
Northern Care Alliance NHS Group /ID# 131156
St George's University Hospitals NHS Foundation Trust /ID# 132301

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

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).

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).

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).

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).

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT02219490

First Posted

August 15, 2014

Last Updated

June 27, 2022

Sponsor

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02219490

Brief Title

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

Acronym

TOPAZ-I

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-I)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

October 30, 2014 (Actual)

Primary Completion Date

May 13, 2021 (Actual)

Study Completion Date

May 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C Virus (HCV) Infection Genotype 1

Keywords

Hepatitis C Genotype 1, Compensated Cirrhosis, Cirrhosis, Naive, Hepatitis C, Hepatitis C Virus, Treatment-Experienced, Relapser, Null responder, Non responder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1596 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ABT-450/r/ABT-267

Other Intervention Name(s)

ABT-450 also known as paritaprevir, ABT-267 also known as ombitasvir, Paritaprevir/ritonavir/ombitasvir also known as Viekirax

Intervention Description

Tablet for oral use

Intervention Type

Drug

Intervention Name(s)

ABT-333

Other Intervention Name(s)

ABT-333 also known as dasabuvir, ABT-333 also known as Exviera

Intervention Description

Tablet for oral use

Intervention Type

Drug

Intervention Name(s)

Ribavirin (RBV)

Intervention Description

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.

Primary Outcome Measure Information:

Title

All-Cause Death: Time to Event

Description

Time Frame