Trial Outcomes & Findings for A Follow-up Assessment of Resistance to ABT-333 in Hepatitis C Virus (HCV)-Infected Subjects Who Have Received ABT-333 in ABT-333 Studies (NCT NCT00726882)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Baseline (day of study completion or early discontinuation from the prior ABT-333 clinical study), 48 weeks

Results posted on

2015-01-08

Participant Flow

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).

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	35
Overall Study Received ABT-333 in Study M10-380	22
Overall Study Received ABT-333 in Study M10-351	6
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Withdrawal by Subject	5
Overall Study Lost to Follow-up	7
Overall Study Other	10

Baseline Characteristics

A Follow-up Assessment of Resistance to ABT-333 in Hepatitis C Virus (HCV)-Infected Subjects Who Have Received ABT-333 in ABT-333 Studies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HCV-infected Participants n=35 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.
Age, Continuous	45.3 years STANDARD_DEVIATION 11.12 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Participants From Study M10-380 n=5 Participants Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level in the prior clinical study (NCT00851890/M10-380) involving ABT-333. Participants received no treatment in this follow-up study.	Participants From Study M10-351 n=4 Participants Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level in the prior clinical study (NCT00696904/M10-351) involving ABT-333. Participants received no treatment in this follow-up study.
Persistence of Resistance-Associated Variants and Phenotypic Resistance Post-Treatment Variants in NS5B (m=5; n=3)	4 participants	0 participants
Persistence of Resistance-Associated Variants and Phenotypic Resistance Post-Treatment Resistance > 10-fold (m=5; n=4)	2 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Participants From Study M10-380 n=35 Participants Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level in the prior clinical study (NCT00851890/M10-380) involving ABT-333. Participants received no treatment in this follow-up study.	Participants From Study M10-351 Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level in the prior clinical study (NCT00696904/M10-351) involving ABT-333. Participants received no treatment in this follow-up study.
Number of Participants With Serious Adverse Events Related to Study Procedures	0 participants	—

Adverse Events

HCV-infected Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Global Medical Services

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

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