Clinical Trials List
Protocol NumberM14-491
NCT Number(ClinicalTrials.gov Identfier)NCT02517528
2015-09-16 - 2017-06-30
Phase III
Terminated5
ICD-10B18.2
Chronic viral hepatitis C
ICD-10B18
Chronic viral hepatitis
ICD-9070.51
Hepatitis C without mention of hepatic coma, acute or unspecified
An Open-Label Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ ABT-267 (ABT-450/r/ABT-267) and ABT-333 Coadministered with Ribavirin (RBV) in Treatment-Naïve and Treatment-Experienced Asian Adults with Genotype 1b Chronic Hepatitis C Virus (HCV) Infection and Compensated Cirrhosis
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳昇弘 Digestive System Department
- Hung-Yao Chen Digestive System Department
- Hsueh-Chou Lai Digestive System Department
- 蘇文邦 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃惠君 Digestive System Department
The Actual Total Number of Participants Enrolled
6 Terminated
Audit
None
Co-Principal Investigator
- Pin-Nan Cheng Digestive System Department
- 吳毅晉 Digestive System Department
- Chiu Hung Chiu Digestive System Department
- 邱彥程 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Ming-Lung Yu Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Jee-Fu Huang Digestive System Department
- Wan-Long Chuang Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chun-Jen Liu Digestive System Department
- PEI-JER CHEN Digestive System Department
- 楊宏志 Digestive System Department
- 蘇東弘 Digestive System Department
- Chen-Hua Liu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Genotype 1b Chronic Hepatitis C Virus (HCV) Infection and Compensated Cirrhosis
Objectives
The primary objectives of this study are to assess the safety and to compare the percentage of subjects
achieving SVR12 rate (the percentage of subjects achieving a 12 week sustained virologic response,
SVR12, [HCV ribonucleic acid (RNA), < lower limit of quantification (LLOQ), 12 weeks following
therapy] and the percentage of subjects achieving SVR24 [HCV RNA < LLOQ, 24 weeks following
therapy] (SVR24 for China only) following 12 weeks of treatment with co-formulated ABT-450, ritonavir
and ABT-267 (ABT-450/r/ABT-267) and ABT-333 coadministered with ribavirin to the historical SVR
rate of telaprevir plus pegIFN and RBV therapy in HCV genotype 1b-infected cirrhotic adults.
The secondary objectives of this study are to demonstrate the effect of the DAA combination regimen on
HCV RNA levels during and after treatment as measured by on-treatment virologic failure and
post-treatment relapse, respectively.
Test Drug
ABT-450/Ritonavir/ABT-267, ABT-333, Ribavirin
Active Ingredient
ABT-333
ABT-450/Ritonavir/ABT-267
Ribavirin
ABT-450/Ritonavir/ABT-267
Ribavirin
Dosage Form
tablet
Dosage
200
250
75/50/12.5
250
75/50/12.5
Endpoints
Efficacy:
Plasma HCV RNA (IU/mL) will be assessed at each Treatment and Post-Treatment Visit.
Patient Reported Outcomes (PROs):
The change in general and disease-specific Health Related Quality of Life (HRQoL) will be assessed
using the SF-36v2 (Short Form 36-Version 2) and HCV Patient Reported Outcomes (HCVPRO)
instruments, respectively. Health State Utility will be measured using the EuroQol-5 Dimensions-5
Level (EQ-5D-5L).
Resistance:
For subjects receiving study drugs who experience virologic failure, the amino acid variants at signature
resistance-associated amino acid positions by population nucleotide sequencing at baseline compared to
the prototypic reference sequence, the amino acid variants by population nucleotide sequencing at
available post-baseline time points compared to baseline, and the amino acid variants at signature
resistance-associated positions by population nucleotide sequencing compared to the prototypic reference
sequence will be tabulated and summarized. In addition, a listing of amino acid variants that emerge in
isolates from at least 2 subjects will be provided, and the persistence of viral resistance-associated amino
acid variants will be summarized.
Pharmacokinetic:
Plasma concentrations for ABT-450, possible ABT-450 metabolites, ritonavir, ABT-267, ABT-267
metabolites ABT-333, ABT-333 M1 metabolite, other possible ABT-333 metabolites and RBV will be
determined at each study visit up to the end of treatment.
Values for the pharmacokinetic parameters of ABT-450, ABT-267, ritonavir, ABT-333, ABT-333 M1
metabolite, and ribavirin including the Cmax, Tmax, Ctrough, and AUC will be determined by
non-compartmental methods using data from subjects who participate in intensive pharmacokinetic
sampling in the study. Additional parameters or summaries may be determined if useful in the
interpretation of the data.
Safety:
Safety and tolerability will be assessed by monitoring adverse events, physical examinations, clinical
laboratory tests, 12-Lead ECGs and vital signs.
Plasma HCV RNA (IU/mL) will be assessed at each Treatment and Post-Treatment Visit.
Patient Reported Outcomes (PROs):
The change in general and disease-specific Health Related Quality of Life (HRQoL) will be assessed
using the SF-36v2 (Short Form 36-Version 2) and HCV Patient Reported Outcomes (HCVPRO)
instruments, respectively. Health State Utility will be measured using the EuroQol-5 Dimensions-5
Level (EQ-5D-5L).
Resistance:
For subjects receiving study drugs who experience virologic failure, the amino acid variants at signature
resistance-associated amino acid positions by population nucleotide sequencing at baseline compared to
the prototypic reference sequence, the amino acid variants by population nucleotide sequencing at
available post-baseline time points compared to baseline, and the amino acid variants at signature
resistance-associated positions by population nucleotide sequencing compared to the prototypic reference
sequence will be tabulated and summarized. In addition, a listing of amino acid variants that emerge in
isolates from at least 2 subjects will be provided, and the persistence of viral resistance-associated amino
acid variants will be summarized.
Pharmacokinetic:
Plasma concentrations for ABT-450, possible ABT-450 metabolites, ritonavir, ABT-267, ABT-267
metabolites ABT-333, ABT-333 M1 metabolite, other possible ABT-333 metabolites and RBV will be
determined at each study visit up to the end of treatment.
Values for the pharmacokinetic parameters of ABT-450, ABT-267, ritonavir, ABT-333, ABT-333 M1
metabolite, and ribavirin including the Cmax, Tmax, Ctrough, and AUC will be determined by
non-compartmental methods using data from subjects who participate in intensive pharmacokinetic
sampling in the study. Additional parameters or summaries may be determined if useful in the
interpretation of the data.
Safety:
Safety and tolerability will be assessed by monitoring adverse events, physical examinations, clinical
laboratory tests, 12-Lead ECGs and vital signs.
Inclution Criteria
Main Inclusion:
1. Male or female of Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean,
and Taiwanese parentage between the ages of 18 and 70 years, inclusive, at the time of Screening.
2. Chronic HCV-infection prior to study enrollment. Chronic HCV-infection is defined as one of the
following:
Positive for anti-HCV antibody (Ab) or HCV RNA > 1000 IU/mL at least 6 months before
Screening, and positive for HCV RNA and anti-HCV Ab at the time of Screening; or
Positive for HCV RNA > 1000 IU/mL at the time of Screening with a liver biopsy consistent
with chronic HCV-infection (or a liver biopsy performed prior to enrollment with evidence of
chronic hepatitis C disease).
3. Screening laboratory result indicating HCV genotype 1b-infection.
4. Compensated cirrhosis defined as a Child-Pugh Score of ≤ 6 at Screening.
5. Per local standard practice, documentation of cirrhosis by one of the following methods:
Diagnosis on previous liver biopsy or liver biopsy conducted during screening e.g., Metavir
Score of > 3 (including 3/4 or 3 – 4), Ishak score of > 4 or,
FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the Screening Period.
1. Male or female of Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean,
and Taiwanese parentage between the ages of 18 and 70 years, inclusive, at the time of Screening.
2. Chronic HCV-infection prior to study enrollment. Chronic HCV-infection is defined as one of the
following:
Positive for anti-HCV antibody (Ab) or HCV RNA > 1000 IU/mL at least 6 months before
Screening, and positive for HCV RNA and anti-HCV Ab at the time of Screening; or
Positive for HCV RNA > 1000 IU/mL at the time of Screening with a liver biopsy consistent
with chronic HCV-infection (or a liver biopsy performed prior to enrollment with evidence of
chronic hepatitis C disease).
3. Screening laboratory result indicating HCV genotype 1b-infection.
4. Compensated cirrhosis defined as a Child-Pugh Score of ≤ 6 at Screening.
5. Per local standard practice, documentation of cirrhosis by one of the following methods:
Diagnosis on previous liver biopsy or liver biopsy conducted during screening e.g., Metavir
Score of > 3 (including 3/4 or 3 – 4), Ishak score of > 4 or,
FibroScan score ≥ 14.6 kPa within 6 months of Screening or during the Screening Period.
Exclusion Criteria
Main Exclusion:
1. HCV genotype performed during screening indicating unable to genotype or infection with any other
HCV genotype.
2. Positive test result at Screening for Hepatitis B surface antigen (HBsAg), or HBV DNA > LLOQ if
HBsAg negative, or anti-Human Immunodeficiency virus antibody (HIV Ab).
3. Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8
within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement
prior to study drug administration.
4. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver
decompensation including ascites (noted on physical exam), variceal bleeding, or hepatic
encephalopathy.
5. Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening.
6. Confirmed presence of hepatocellular carcinoma (HCC) indicated on imaging techniques such as
computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to
Screening or on an ultrasound performed at Screening (a positive ultrasound result should be
confirmed with CT scan or MRI.)
7. Any primary cause of liver disease other than chronic HCV-infection, including but not limited to
the following:
Hemochromatosis
Alpha-1 antitrypsin deficiency
Wilson's disease
Autoimmune hepatitis
Alcoholic liver disease
Drug-related liver disease
Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related changes would not
be considered exclusionary unless the steatohepatitis is considered to be the primary cause of the
liver disease.
8. Screening laboratory analyses showing any of the following abnormal laboratory results:
Alanine aminotransferase (ALT) > 7 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) > 7 × ULN
Estimated Glomerular filtration rate adjusted for the Asian population (eGFR)
< 50 mL/min/1.73m2 as estimated by the C-MDRD method, modified for the Asian population,
according to the following formula: eGFR = 175 × (Serum Creatinine) –1.234 × (Age) –0.179 ×
(0.79 if Female)
Albumin < 2.8 g/dL
International normalized ratio (INR) > 2.3. Subjects with a known inherited blood disorder and
INR > 2.3 may be enrolled with permission of the AbbVie Study Designated Physician
Hemoglobin < LLN
Platelets < 60,000 cells per mm3
Absolute neutrophil count (ANC) < 1200 cells/μL
Total bilirubin ≥ 3.0 mg/dL
1. HCV genotype performed during screening indicating unable to genotype or infection with any other
HCV genotype.
2. Positive test result at Screening for Hepatitis B surface antigen (HBsAg), or HBV DNA > LLOQ if
HBsAg negative, or anti-Human Immunodeficiency virus antibody (HIV Ab).
3. Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8
within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement
prior to study drug administration.
4. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver
decompensation including ascites (noted on physical exam), variceal bleeding, or hepatic
encephalopathy.
5. Serum Alpha-Fetoprotein (sAFP) > 100 ng/mL at Screening.
6. Confirmed presence of hepatocellular carcinoma (HCC) indicated on imaging techniques such as
computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to
Screening or on an ultrasound performed at Screening (a positive ultrasound result should be
confirmed with CT scan or MRI.)
7. Any primary cause of liver disease other than chronic HCV-infection, including but not limited to
the following:
Hemochromatosis
Alpha-1 antitrypsin deficiency
Wilson's disease
Autoimmune hepatitis
Alcoholic liver disease
Drug-related liver disease
Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related changes would not
be considered exclusionary unless the steatohepatitis is considered to be the primary cause of the
liver disease.
8. Screening laboratory analyses showing any of the following abnormal laboratory results:
Alanine aminotransferase (ALT) > 7 × upper limit of normal (ULN)
Aspartate aminotransferase (AST) > 7 × ULN
Estimated Glomerular filtration rate adjusted for the Asian population (eGFR)
< 50 mL/min/1.73m2 as estimated by the C-MDRD method, modified for the Asian population,
according to the following formula: eGFR = 175 × (Serum Creatinine) –1.234 × (Age) –0.179 ×
(0.79 if Female)
Albumin < 2.8 g/dL
International normalized ratio (INR) > 2.3. Subjects with a known inherited blood disorder and
INR > 2.3 may be enrolled with permission of the AbbVie Study Designated Physician
Hemoglobin < LLN
Platelets < 60,000 cells per mm3
Absolute neutrophil count (ANC) < 1200 cells/μL
Total bilirubin ≥ 3.0 mg/dL
The Estimated Number of Participants
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Taiwan
20 participants
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Global
100 participants
