HCV Infection
Conditions
Keywords
HCV Infection
Brief summary
The purpose of this follow-up study is to evaluate the frequency and persistence of specific viral mutations in response to treatment with ABT-333 (dasabuvir).
Detailed description
This Phase 2, multicenter study was conducted in HCV-infected participants who received ABT-333 at any dose level or matching placebo in a prior clinical study involving ABT-333. Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level or matching placebo in Study M10-351 Substudy 2 (NCT00696904; ABT-333 dosing duration was 2 days) and Study M10-380 (NCT00851890; ABT-333 dosing duration was 28 days) were eligible. After receiving at least 1 dose of ABT-333 or placebo, subjects were assessed for participation in this rollover study and asked to review the informed consent. The day of study completion or early discontinuation from the prior ABT-333 clinical study served as the baseline assessment. If it was found that a participant received placebo during the previous ABT-333 clinical study, the sites were instructed to discontinue the participant from this study. This study included approximately monthly blood sample collection procedures for 48 weeks, and no treatment was provided during this time.
Interventions
PROCEDUREBlood sample collection only
Approximately monthly collection of blood samples.
DRUGABT-333
Previous treatment in prior ABT-333 studies.
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Main Selection Criteria: Subject received ABT-333 or matching placebo in a prior clinical study involving ABT-333.
Exclusion criteria
\- The investigator considers the subject unsuitable for the study for any reasons inclusive of, but not limited to, failure to comply with study procedures in prior ABT-333 clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Persistence of Resistance-Associated Variants and Phenotypic Resistance | Baseline (day of study completion or early discontinuation from the prior ABT-333 clinical study), 48 weeks | Participants in studies M10-351 (NCT00851890) and M10-380 (NCT00696904) were analyzed for persistence of resistance-associated variants by comparing post-treatment clonal sequence data with baseline and on-treatment sequence data from M10-351 and M10-380 studies to assess amino acid changes. Phenotypic resistance to ABT-333 was assessed by calculating the fold change in half maximal effective concentration (EC50) of post-treatment samples compared with the EC50 value for the corresponding baseline sample as determined for M10-351 and M10-380 studies. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at post-treatment time points are presented. Variants are included if the absolute percent of total clones encoding the variant was at least 10% greater than at baseline in a post-treatment sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events Related to Study Procedures | 48 weeks | Only serious adverse events that the investigator considered causally related to study procedures (i.e., venipuncture) were to be collected in this study. A serious adverse event was defined as any untoward medical occurrence in a clinical investigation subject that the investigator believed to be causally related to a study procedure and met at least 1 of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, congenital anomaly, persistent or significant disability/incapacity, important medical event requiring medical or surgical intervention to prevent serious outcome, elective or spontaneous abortion. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level or matching placebo in Study M10-351 Substudy 2 (NCT00696904) or Study M10-380 (NCT00851890).
Participants by arm
| Arm | Count |
|---|---|
| HCV-infected Participants Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level or matching placebo in a prior clinical study involving ABT-333.
Participants received no treatment in this follow-up study. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Other | 10 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | HCV-infected Participants |
|---|---|
| Age, Continuous | 45.3 years STANDARD_DEVIATION 11.12 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
Persistence of Resistance-Associated Variants and Phenotypic Resistance
Participants in studies M10-351 (NCT00851890) and M10-380 (NCT00696904) were analyzed for persistence of resistance-associated variants by comparing post-treatment clonal sequence data with baseline and on-treatment sequence data from M10-351 and M10-380 studies to assess amino acid changes. Phenotypic resistance to ABT-333 was assessed by calculating the fold change in half maximal effective concentration (EC50) of post-treatment samples compared with the EC50 value for the corresponding baseline sample as determined for M10-351 and M10-380 studies. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at post-treatment time points are presented. Variants are included if the absolute percent of total clones encoding the variant was at least 10% greater than at baseline in a post-treatment sample.
Time frame: Baseline (day of study completion or early discontinuation from the prior ABT-333 clinical study), 48 weeks
Population: Resistance analyses included all participants who received ABT-333 in the previous study who had sufficient HCV RNA recovered from samples collected during this study for genotypic and phenotypic analysis to proceed. m, n = the number of evaluable participants for the analysis specified for M10-380 and M10-351, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants From Study M10-380 | Persistence of Resistance-Associated Variants and Phenotypic Resistance | Post-Treatment Variants in NS5B (m=5; n=3) | 4 participants |
| Participants From Study M10-380 | Persistence of Resistance-Associated Variants and Phenotypic Resistance | Post-Treatment Resistance > 10-fold (m=5; n=4) | 2 participants |
| Participants From Study M10-351 | Persistence of Resistance-Associated Variants and Phenotypic Resistance | Post-Treatment Variants in NS5B (m=5; n=3) | 0 participants |
| Participants From Study M10-351 | Persistence of Resistance-Associated Variants and Phenotypic Resistance | Post-Treatment Resistance > 10-fold (m=5; n=4) | 0 participants |
Secondary
Number of Participants With Serious Adverse Events Related to Study Procedures
Only serious adverse events that the investigator considered causally related to study procedures (i.e., venipuncture) were to be collected in this study. A serious adverse event was defined as any untoward medical occurrence in a clinical investigation subject that the investigator believed to be causally related to a study procedure and met at least 1 of the following criteria: death, life-threatening, hospitalization or prolongation of hospitalization, congenital anomaly, persistent or significant disability/incapacity, important medical event requiring medical or surgical intervention to prevent serious outcome, elective or spontaneous abortion.
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants From Study M10-380 | Number of Participants With Serious Adverse Events Related to Study Procedures | 0 participants |