Trial Outcomes & Findings for Study of the Anti-HCV Drug (BMS-790052) Combined With Peginterferon and Ribavirin in Patients Who Failed Prior Treatment (NCT NCT01170962)

Last Updated: 2015-10-12

Results Overview

eRVR was defined as undetectable Hepatitis C virus RNA at both Weeks 4 and 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

512 participants

Primary outcome timeframe

Week 4, Week 12

Results posted on

2015-10-12

Participant Flow

Participants were enrolled at 69 sites in 11 countries.

A total of 512 participants were enrolled and 421 participants were randomized (2 randomized participants were not treated: 1 due to positive pregnancy test and 1 no longer met criteria). Remaining 91 participants were not randomized as; 73 no longer met study criteria, 15 withdrew consent, 1 due to administrative reason and 2 for other reasons.

Participant milestones

Participant milestones
Measure	Daclatasvir (20 mg): Prior Null and Partial Responders Participants (prior null or partial responders) received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null and Partial Responders Participants (prior null or partial responders) received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Treatment Period STARTED	203	199	17
Treatment Period No PDR	145	127	17
Treatment Period PDR -Randomized to 24 Weeks pegIFNα--2a	30	36	0
Treatment Period PDR -Randomized to 48 Weeks Follow--up	28	36	0
Treatment Period COMPLETED	76	88	5
Treatment Period NOT COMPLETED	127	111	12
Follow up Period STARTED	198	192	15
Follow up Period COMPLETED	159	165	9
Follow up Period NOT COMPLETED	39	27	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Daclatasvir (20 mg): Prior Null and Partial Responders Participants (prior null or partial responders) received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null and Partial Responders Participants (prior null or partial responders) received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Treatment Period Lack of Efficacy	96	91	7
Treatment Period Adverse Event	11	12	3
Treatment Period Withdrawal by Subject	2	1	0
Treatment Period Lost to Follow-up	1	1	1
Treatment Period Participant no longer meets criteria	0	1	0
Treatment Period Request to discontinue treatment	7	3	1
Treatment Period Completed 24 Week treatment period only	10	2	0
Follow up Period Withdrawal by Subject	14	10	2
Follow up Period Lost to Follow-up	13	8	1
Follow up Period Death	2	2	0
Follow up Period Others	10	7	3

Baseline Characteristics

Study of the Anti-HCV Drug (BMS-790052) Combined With Peginterferon and Ribavirin in Patients Who Failed Prior Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daclastavir (20mg): Prior Null and Partial Responders n=203 Participants Participants (prior null or partial responders) received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclastavir (60mg): Prior Null and Partial Responders n=199 Participants Participants (prior null or partial responders) received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Total n=419 Participants Total of all reporting groups
Age, Customized 21-65 years	192 participants n=5 Participants	189 participants n=7 Participants	15 participants n=5 Participants	396 participants n=4 Participants
Age, Customized >=65 years	11 participants n=5 Participants	10 participants n=7 Participants	2 participants n=5 Participants	23 participants n=4 Participants
Sex: Female, Male Female	70 Participants n=5 Participants	72 Participants n=7 Participants	4 Participants n=5 Participants	146 Participants n=4 Participants
Sex: Female, Male Male	133 Participants n=5 Participants	127 Participants n=7 Participants	13 Participants n=5 Participants	273 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 4, Week 12

Population: All treated participants who received at least 1 dose of study therapy.

eRVR was defined as undetectable Hepatitis C virus RNA at both Weeks 4 and 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=133 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=132 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=70 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=67 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	18.0 percentage of participants Interval 13.8 to 22.3	19.7 percentage of participants Interval 15.3 to 24.1	25.7 percentage of participants Interval 19.0 to 32.4	35.8 percentage of participants Interval 28.3 to 43.3	0 percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: Follow-up Week 24

Population: All treated participants who received at least 1 dose of study therapy.

SVR24 was defined as undetectable RNA (Hepatitis C Virus \[HCV\] RNA \<lower limit of quantitation \[LLOQ\], target not detected \[TND\]) at follow-up Week 24. TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=133 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=132 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=70 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=67 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Percentage of Participants With 24-week Sustained Virologic Response (SVR24)	18.8 percentage of participants Interval 14.5 to 23.1	22.0 percentage of participants Interval 17.4 to 26.6	24.3 percentage of participants Interval 17.7 to 30.9	43.3 percentage of participants Interval 35.5 to 51.0	0 percentage of participants Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: From first dose to last dose plus 7 days, up to 49 weeks

Population: Safety population included all treated participants.

AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity; or was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=203 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=199 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=17 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died On-treatment SAEs	14 participants	11 participants	3 participants	—	—
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died On-treatment AEs Leading to Discontinuation of Treatment	11 participants	12 participants	3 participants	—	—
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died On-treatment Death	0 participants	0 participants	1 participants	—	—

PRIMARY outcome

Timeframe: From day 8 post last dose of treatment up-to Week 72

Population: Safety population included all treated participants.

AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=198 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=192 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=15 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Number of Participants With Serious Adverse Events (SAEs) and Who Died During Follow-up Period SAEs	6 participants	7 participants	0 participants	—	—
Number of Participants With Serious Adverse Events (SAEs) and Who Died During Follow-up Period Death	2 participants	2 participants	0 participants	—	—

SECONDARY outcome

Timeframe: Week 4

Population: All treated participants who received at least 1 dose of study therapy.

RVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA \<lower limit of quantitation \[LLOQ\], target not detected (TND) at Week 4. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=133 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=132 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=70 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=67 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Percentage of Participants With Rapid Virologic Response (RVR)	21.8 percentage of participants Interval 17.2 to 26.4	21.2 percentage of participants Interval 16.7 to 25.8	25.7 percentage of participants Interval 19.0 to 32.4	38.8 percentage of participants Interval 31.2 to 46.4	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Week 12

Population: All treated participants who received at least 1 dose of study therapy.

cEVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA \<lower limit of quantitation \[LLOQ\], target not detected (TND) at Week 12. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=133 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=132 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=70 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=67 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Percentage of Participants With Complete Early Virologic Response (cEVR)	30.1 percentage of participants Interval 25.0 to 35.2	34.1 percentage of participants Interval 28.8 to 39.4	44.3 percentage of participants Interval 36.7 to 51.9	56.7 percentage of participants Interval 49.0 to 64.5	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Follow-up Week 12

Population: All treated participants who received at least 1 dose of study therapy.

SVR12 was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA \<lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=133 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=132 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=70 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=67 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 Participants Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12)	19.5 percentage of participants Interval 15.1 to 24.0	23.5 percentage of participants Interval 18.8 to 28.2	25.7 percentage of participants Interval 19.0 to 32.4	47.8 percentage of participants Interval 39.9 to 55.6	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline to follow-up Week 48

Population: All treated participants who received at least 1 dose of study therapy.

Non-structural protein 5A of HCV resistance associated polymorphism in GT-1a samples included M28L/T/V, Q30H, L31M, H54Y, H58C/D/N/P/Q, E62D and Y93C.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=83 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=86 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=50 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=37 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H58: C/D/N/P/Q: Relapsers (n=10,12,7,3)	0 participants	0 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures E62: D: Baseline (n=78,84,49,0)	1 participants	3 participants	2 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures E62: D: On-Treatment (n= 60,57,34,0)	1 participants	2 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures E62: D: Relapsers (n=10,12,7,0)	0 participants	1 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: C: Baseline (n=0,84,49,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	1 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: C: On-Treatment (n= 0,57,34,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	1 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: C: Relapsers (n=0,12,7,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures M28: L/T/V: Baseline (n=78,84,49,36)	2 participants	3 participants	1 participants	3 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures M28: L/T/V: On-Treatment (n= 60,57,34,22)	2 participants	3 participants	1 participants	2 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures M28: L/T/V: Relapsers (n=10,12,7,3)	0 participants	0 participants	0 participants	0 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q30: H: Baseline (n=78,0,0,36)	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	1 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q30: H: On-Treatment (n= 60,0,0,22)	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q30: H:Relapsers (n=10,0,0,3)	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: Baseline (n=78,84,49,36)	5 participants	1 participants	1 participants	2 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: On-Treatment (n= 60,57,34,22)	5 participants	1 participants	0 participants	2 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: Relapsers (n=10,12,7,3)	0 participants	0 participants	1 participants	0 participants	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H54: Y: Baseline (n=0,84,49,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	2 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H54: Y: On-Treatment (n=0,57,34,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	2 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H54: Y: Relapsers (n=0,12,7,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H58: C/D/N/P/Q: Baseline (n=78,84,49,0)	4 participants	3 participants	3 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures H58: C/D/N/P/Q: On-Treatment (n= 60,57,34,0)	4 participants	3 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—

SECONDARY outcome

Timeframe: Baseline to follow-up Week 48

Population: All treated participants who received at least 1 dose of study therapy.

Non-structural protein 5A of HCV resistance associated polymorphisms in GT-1b samples, included L28M/V, R30H/Q, L31M, Q54H/N/Y, P58A/Q/S, Q62E/K/N/R/S, A92T/V and Y93F/H.

Outcome measures

Outcome measures
Measure	Daclatasvir (20 mg): Prior Null Responders n=44 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null Responders n=38 Participants Participants received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (20 mg): Prior Partial Responders n=20 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Partial Responders n=29 Participants Participants received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L28: M/V: Baseline (n=43,37,19,0)	1 participants	1 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L28: M/V: On-Treatment (n=19,20,6,0)	1 participants	1 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L28: M/V: Relapsers (n=7,6,2,0)	0 participants	0 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures R30: H/Q: Baseline (n=43,37,19,27)	4 participants	5 participants	1 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures R30: H/Q: On-Treatment (n=19,20,6,5)	4 participants	3 participants	0 participants	0 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures R30: H/Q: Relapsers (n=7,6,2,9)	0 participants	2 participants	1 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: Baseline (n=43,37,19,27)	4 participants	5 participants	1 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: On-Treatment (n=19,20,6,5)	2 participants	4 participants	0 participants	0 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures L31: M: Relapsers (n=7,6,2,9)	1 participants	0 participants	1 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q54: H/N/Y: Baseline (n=43,37,19,27)	18 participants	20 participants	9 participants	8 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q54: H/N/Y: On-Treatment (n=19,20,6,5)	9 participants	12 participants	5 participants	2 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q54: H/N/Y: Relapsers (n=7,6,2,9)	5 participants	1 participants	0 participants	2 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures P58: A/Q/S: Baseline (n=43,37,19,27)	3 participants	7 participants	2 participants	3 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures P58: A/Q/S: On-Treatment (n=19,20,6,5)	2 participants	3 participants	1 participants	0 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures P58: A/Q/S: Relapsers (n=7,6,2,9)	0 participants	2 participants	0 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q62: E/K/N/R/S: Baseline (n=43,37,19,27)	5 participants	1 participants	2 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q62: E/K/N/R/S: On-Treatment (n=19,20,6,5)	3 participants	1 participants	1 participants	0 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Q62: E/K/N/R/S: Relapsers (n=7,6,2,9)	0 participants	0 participants	0 participants	1 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures A92: T/V: Baseline (n=43,37,19,0)	2 participants	3 participants	3 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures A92: T/V: On-Treatment (n=0,20,6,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	2 participants	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures A92: T/V: Relapsers (n=0,6,2,0)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	0 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: F/H: Baseline (n=43,37,0,27)	1 participants	5 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	3 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: F/H: On-Treatment (n=0,20,0,5)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	4 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	0 participants	—
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures Y93: F/H: Relapsers (n=0,6,0,9)	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	1 participants	NA participants Data was not analyzed as no participant was evaluable at the specified time-point.	2 participants	—

Adverse Events

Daclatasvir (20 mg): Prior Null and Partial Responders

Serious events: 14 serious events

Other events: 190 other events

Deaths: 0 deaths

Daclatasvir (60 mg): Prior Null and Partial Responders

Serious events: 11 serious events

Other events: 195 other events

Deaths: 0 deaths

Placebo: Prior Partial Responders

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Daclatasvir (20 mg): Prior Null and Partial Responders n=203 participants at risk Participant (prior null or partial responders) received daclatasvir tablets 20 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Daclatasvir (60 mg): Prior Null and Partial Responders n=199 participants at risk Participant (prior null or partial responders) received daclatasvir tablets 60 mg orally once daily, pegylated-interferon alfa-2a (pegIFNα-2a) injection 180 µg/0.5 mL subcutaneously once weekly, ribavirin tablets 1000-1200 mg orally twice daily for 24 weeks. At Week 24, participants with a protocol defined response (PDR: HCV RNA \<LOQ at Week 4, undetectable HCV RNA at Week 12) were randomized (1:1) to either a follow-up period of 48 weeks or received pegIFNα-2a and ribavirin for 24 weeks and then followed for 24 weeks. Participants with no PDR continued to receive pegIFNα-2a and ribavirin, for an additional 24 weeks and followed up for 24 weeks. Prior null responders: \<1 log10 HCV RNA decrease from baseline at or after 4 weeks, or \<2 log10 decrease from baseline in HCV RNA at or after Week 12 of IFN-based therapy. Prior Partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.	Placebo: Prior Partial Responders n=17 participants at risk Participants who were prior partial responders received placebo matched with daclatasvir tablets orally, once daily for 24 weeks. Participants received pegIFNα-2a 180 µg/0.5 mL subcutaneously, once weekly, and ribavirin tablets 1000-1200 mg orally, twice daily for 48 weeks and followed post treatment for 24 weeks. Prior partial responders: \>2 log10 decrease in HCV RNA from baseline at Week 12 of IFN-based therapy but detectable HCV RNA when therapy was discontinued.
Blood and lymphatic system disorders Anaemia	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Cardiac disorders Angina unstable	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Renal and urinary disorders Bladder perforation	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Gastroenteritis	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Nervous system disorders Ischaemic stroke	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Injury, poisoning and procedural complications Laceration	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Pneumonia	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Cat scratch disease	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Nervous system disorders Lacunar infarction	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Lung infection	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Injury, poisoning and procedural complications Rib fracture	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Investigations Streptococcus test positive	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Blood and lymphatic system disorders Anaemia haemolytic autoimmune	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Nervous system disorders Hepatic encephalopathy	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Nervous system disorders Cerebrovascular accident	0.99% 2/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Gastrointestinal disorders Duodenal ulcer	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Blood and lymphatic system disorders Pancytopenia	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Vascular disorders Deep vein thrombosis	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
General disorders Influenza like illness	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Eye disorders Retinal exudates	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Eye disorders Retinal haemorrhage	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Hepatobiliary disorders Hepatic failure	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Gastrointestinal disorders Pancreatitis	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Postoperative wound infection	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Psychiatric disorders Substance abuse	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Ear and labyrinth disorders Vertigo	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Gastrointestinal disorders Anal fissure	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.50% 1/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
General disorders Pyrexia	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Renal and urinary disorders Renal failure acute	0.00% 0/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	5.9% 1/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period
Infections and infestations Staphylococcal sepsis	0.49% 1/203 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/199 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period	0.00% 0/17 • From first dose to last dose plus 7 days, up to 49 weeks On-Treatment Period