Trial Outcomes & Findings for A Study to Assess Resistance and Durability of Response to ABT-493 and/or ABT-530 (NCT NCT02441283)
NCT ID: NCT02441283
Last Updated: 2020-09-21
Results Overview
Maintaining a sustained virologic response (SVR) is defined as having Hepatitis C virus ribonucleic acid (HCV RNA) value consistently below the lower limit of quantification (\< LLOQ) from the end of treatment in the previous study throughout Study M13-576 (this study).
COMPLETED
PHASE2/PHASE3
384 participants
From the end of treatment in the previous study up to 3 years post-treatment
2020-09-21
Participant Flow
Full Analysis Set (FAS): all participants who received ABT-493 and/or ABT-530 in a prior Phase 2/3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-530 in a prior study were excluded from the FAS.
Participant milestones
| Measure |
HCV-infected Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
|
Overall Study
STARTED
|
377
|
|
Overall Study
COMPLETED
|
287
|
|
Overall Study
NOT COMPLETED
|
90
|
Reasons for withdrawal
| Measure |
HCV-infected Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
|
Overall Study
Withdrew consent
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15
|
|
Overall Study
Lost to Follow-up
|
42
|
|
Overall Study
Death
|
1
|
|
Overall Study
Other, not specified
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32
|
Baseline Characteristics
A Study to Assess Resistance and Durability of Response to ABT-493 and/or ABT-530
Baseline characteristics by cohort
| Measure |
HCV-infected Participants
n=377 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study. The baseline data presented below are values at the time of the prior study start.
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|---|---|
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Age, Continuous
|
54.1 years
STANDARD_DEVIATION 10.96 • n=5 Participants
|
|
Sex: Female, Male
Female
|
172 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
205 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
328 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
29 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multi race
|
1 Participants
n=5 Participants
|
|
HCV Genotype
1
|
168 Participants
n=5 Participants
|
|
HCV Genotype
2
|
76 Participants
n=5 Participants
|
|
HCV Genotype
3
|
106 Participants
n=5 Participants
|
|
HCV Genotype
4
|
14 Participants
n=5 Participants
|
|
HCV Genotype
5
|
7 Participants
n=5 Participants
|
|
HCV Genotype
6
|
6 Participants
n=5 Participants
|
|
Baseline Cirrhosis Status
Yes
|
65 Participants
n=5 Participants
|
|
Baseline Cirrhosis Status
No
|
312 Participants
n=5 Participants
|
|
Treatment Status Prior to Previous Study
Naive
|
265 Participants
n=5 Participants
|
|
Treatment Status Prior to Previous Study
PRS-experienced
|
83 Participants
n=5 Participants
|
|
Treatment Status Prior to Previous Study
NS5A-experienced/PI naive
|
10 Participants
n=5 Participants
|
|
Treatment Status Prior to Previous Study
NS5A- and PI- experienced
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12 Participants
n=5 Participants
|
|
Treatment Status Prior to Previous Study
PI-experienced/NS5A naive
|
7 Participants
n=5 Participants
|
|
Baseline HIV-1/HCV coinfection status
Yes
|
7 Participants
n=5 Participants
|
|
Baseline HIV-1/HCV coinfection status
No
|
370 Participants
n=5 Participants
|
|
Baseline injection drug use status
Yes
|
181 Participants
n=5 Participants
|
|
Baseline injection drug use status
No
|
193 Participants
n=5 Participants
|
|
Baseline injection drug use status
Missing
|
3 Participants
n=5 Participants
|
|
Baseline HCV RNA level
|
6.2573 log10 IU/mL
STANDARD_DEVIATION 0.82900 • n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-450/r + ABT-530 + RBV-12 wks
|
4 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 200 mg QD + ABT-530 40 mg QD-12 wks
|
34 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 200 mg QD + ABT-530 80 mg QD-12 wks
|
1 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 200 mg QD + ABT-530 120 mg QD-12 wks
|
57 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 200 mg QD + ABT-530 120 mg QD + RBV-12 wks
|
10 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 300 mg QD + ABT-530 120 mg QD-8 wks
|
13 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 300 mg QD + ABT-530 120 mg QD-12 wks
|
20 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 300 mg QD + ABT-530 120 mg QD-16 wks
|
1 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493 300 mg QD + ABT-530 120 mg QD + RBV-12 wks
|
5 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493/ABT-530 300 mg/120 mg QD- 8 wks
|
74 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493/ABT-530 300 mg/120 mg QD-12 wks
|
134 Participants
n=5 Participants
|
|
Study Drug Regimens Received in Prior Abbvie Study
ABT-493/ABT-530 300 mg/120 mg QD-16 wks
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the end of treatment in the previous study up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-530 in a prior study were excluded from the FAS.
Maintaining a sustained virologic response (SVR) is defined as having Hepatitis C virus ribonucleic acid (HCV RNA) value consistently below the lower limit of quantification (\< LLOQ) from the end of treatment in the previous study throughout Study M13-576 (this study).
Outcome measures
| Measure |
HCV-infected Participants
n=376 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Percentage of Participants Who Maintained a Sustained Virologic Response (SVR) Out of Those Who Achieved SVR12 in a Prior Study With an ABT-493- and/or ABT-530-containing Regimen
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99.5 percentage of participants
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PRIMARY outcome
Timeframe: From the end of treatment in the previous study up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-530 in a prior study were excluded from the FAS.
Relapse was defined as confirmed Hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between end of treatment and up to and including the last HCV RNA measurement collected in this study for a participant with HCV RNA \< LLOQ at Final Treatment Visit who completed treatment, excluding reinfection. HCV reinfection was defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA \< LLOQ at Final Treatment Visit, along with the post-treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences.
Outcome measures
| Measure |
HCV-infected Participants
n=376 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Percentage of Participants Who Relapsed or Had a New Hepatitis C Virus (HCV) Infection at Any Time up to the Last Follow-up in This Study Among Participants Who Achieved SVR12 in a Prior Study With an ABT-493- and/or ABT-530-containing Regimen
Relapse overall
|
0.3 percentage of participants
|
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Percentage of Participants Who Relapsed or Had a New Hepatitis C Virus (HCV) Infection at Any Time up to the Last Follow-up in This Study Among Participants Who Achieved SVR12 in a Prior Study With an ABT-493- and/or ABT-530-containing Regimen
Reinfection overall
|
0.3 percentage of participants
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PRIMARY outcome
Timeframe: From Day 1 to Month 12Population: Participants who experienced virologic failure in previous study or in the current study with available sequencing data for NS3/4A and/or NS5A
Plasma samples for HCV resistance testing were collected at study visits. The variants in nonstructural viral protein 3 (NS3) and nonstructural viral protein 5A (NS5A) at amino acid positions of interest were analyzed by next generation sequencing relative to baseline and prototypic reference sequences.
Outcome measures
| Measure |
HCV-infected Participants
n=1 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Number of Participants With Persistence of Resistance-Associated Amino Acid Variants Among Those Experiencing Virologic Failure
NS3 Variants at Months 3, 6, and 12
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1 participants
|
|
Number of Participants With Persistence of Resistance-Associated Amino Acid Variants Among Those Experiencing Virologic Failure
NS5A Variants at Months 3, 6, and 12
|
1 participants
|
SECONDARY outcome
Timeframe: After Day 1 up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-530 in a prior study were excluded from the FAS.
Any events (i.e., diagnoses) related to liver disease progression and/or HCV infection considered to be clinically significant by the investigator that began or worsened after Day 1 were documented until the end of the study or initiation of re-treatment for HCV (if applicable). Significant events related to liver disease progression include the development of cirrhosis, events indicative of hepatic decompensation, (including: variceal bleeding, new ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome, hepatic hydrothorax or other evidence of hepatic decompensation considered to be significant by the investigator), change in the Child-Pugh category (e.g., change from Child-Pugh Class A to Child-Pugh Class B), the occurrence of hepatocellular carcinoma, liver transplantation and/or death.
Outcome measures
| Measure |
HCV-infected Participants
n=377 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Medical events related to liver disease or HCV inf
|
7 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Development of cirrhosis
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0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (Variceal bleeding)
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0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (Ascites)
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decomp (spontaneous bacterial peritonitis)
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (hepatic encephalopathy)
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (hepatorenal syndrome)
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (hepatic hydrothorax)
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver decompensation (other [PI's discretion])
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Change in Child-Pugh Score in subject w/cirrhosis
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0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Hepatocellular carcinoma (HCC)
|
5 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Liver transplantation occurred
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0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Death
|
0 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Regenerated node in the liver
|
1 Participants
|
|
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection
Cholangiocarcinoma/differentiated adenocarcinoma
|
1 Participants
|
SECONDARY outcome
Timeframe: From Day 1 up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-530 in a prior study were excluded from the FAS.
A plasma sample for IP-10 testing was collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). IP-10 is used to assess liver fibrosis in participants with chronic liver disease.
Outcome measures
| Measure |
HCV-infected Participants
n=374 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Day 1
|
146.884 ng/L
Standard Deviation 116.6272
|
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Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 3
|
147.606 ng/L
Standard Deviation 118.5143
|
|
Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 6
|
148.959 ng/L
Standard Deviation 119.0047
|
|
Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 12
|
224.400 ng/L
|
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Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 18
|
133.300 ng/L
Standard Deviation 50.2647
|
|
Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 24
|
140.185 ng/L
Standard Deviation 97.2769
|
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Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 30
|
164.244 ng/L
Standard Deviation 276.9176
|
|
Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time
Month 36
|
120.600 ng/L
|
SECONDARY outcome
Timeframe: From Day 1 up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-540 in a prior study were excluded from the FAS.
A serum sample for FibroTest evaluation was collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). FibroTest uses six biomarkers to generate a score that correlates to the degree of liver damage in participants. Scores range from 0 to 1, with higher scores indicating more severe liver fibrosis.
Outcome measures
| Measure |
HCV-infected Participants
n=367 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
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|---|---|
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Mean FibroTest Score Over Time
Day 1
|
0.354 units on a scale
Standard Deviation 0.2341
|
|
Mean FibroTest Score Over Time
Month 3
|
0.363 units on a scale
Standard Deviation 0.2383
|
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Mean FibroTest Score Over Time
Month 6
|
0.353 units on a scale
Standard Deviation 0.2311
|
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Mean FibroTest Score Over Time
Month 12
|
0.405 units on a scale
Standard Deviation 0.0919
|
|
Mean FibroTest Score Over Time
Month 18
|
0.272 units on a scale
Standard Deviation 0.1281
|
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Mean FibroTest Score Over Time
Month 24
|
0.321 units on a scale
Standard Deviation 0.2156
|
|
Mean FibroTest Score Over Time
Month 30
|
0.261 units on a scale
Standard Deviation 0.1667
|
|
Mean FibroTest Score Over Time
Month 36
|
0.190 units on a scale
|
SECONDARY outcome
Timeframe: From Day 1 up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study. Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-540 in a prior study were excluded from the FAS.
A serum sample for aspartate transaminase evaluation and platelets were collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). The aspartate transaminase to platelet ratio index (APRI) is used to assess liver fibrosis in participants with chronic liver disease. Scores range from 0 to ≥ 2.0, with scores \< 0.5 predictive of no liver fibrosis; scores \>1.5 significant fibrosis; and scores \> 2.0 indicative of cirrhosis.
Outcome measures
| Measure |
HCV-infected Participants
n=367 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
|
|---|---|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Day 1
|
0.317 ratio
Standard Deviation 0.2268
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 3
|
0.303 ratio
Standard Deviation 0.2171
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 6
|
0.298 ratio
Standard Deviation 0.2101
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 12
|
0.230 ratio
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 18
|
0.262 ratio
Standard Deviation 0.0589
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 24
|
0.275 ratio
Standard Deviation 0.1620
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 30
|
0.227 ratio
Standard Deviation 0.1084
|
|
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time
Month 36
|
0.215 ratio
Standard Deviation 0.1768
|
SECONDARY outcome
Timeframe: Up to 3 years post-treatmentPopulation: Full Analysis Set (FAS):all participants who received ABT-493 and/or ABT-530 in a prior Phase 2 /3 study and were not retreated prior to enrolling in this study.Three participants who received retreatment prior to enrollment in this study and four participants who did not receive ABT-493 and/or ABT-540 in a prior study were excluded from the FAS.
The FibroScan test is used to assess liver fibrosis in participants with chronic liver disease. This was not performed as a study procedure, but any available results from source documents were summarized. 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.
Outcome measures
| Measure |
HCV-infected Participants
n=23 Participants
Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.
|
|---|---|
|
Mean FibroScan Scores Over Time
Day 1
|
13.014 kPa
Standard Deviation 12.6850
|
|
Mean FibroScan Scores Over Time
Month 3
|
6.880 kPa
Standard Deviation 4.6677
|
|
Mean FibroScan Scores Over Time
Month 6
|
10.780 kPa
Standard Deviation 5.9260
|
|
Mean FibroScan Scores Over Time
Month 12
|
7.700 kPa
Standard Deviation 4.2208
|
|
Mean FibroScan Scores Over Time
Month 18
|
6.913 kPa
Standard Deviation 2.8002
|
|
Mean FibroScan Scores Over Time
Month 24
|
6.757 kPa
Standard Deviation 3.1564
|
|
Mean FibroScan Scores Over Time
Month 30
|
9.400 kPa
|
Adverse Events
HCV-infected Participants-- FAS
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER