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Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus

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ClinicalTrials.gov Identifier: NCT01628692
Recruitment Status : Completed
First Posted : June 27, 2012
Results First Posted : November 30, 2015
Last Update Posted : February 23, 2017
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus
Interventions Drug: Daclatasvir
Drug: Simeprevir
Drug: Ribavirin
Enrollment 230
Recruitment Details The study was conducted at 25 centers in 6 countries.
Pre-assignment Details Of the 230 participants enrolled, 168 received treatment.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period. Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up. Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up. Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period. Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks. Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Period Title: Overall Study
Started 53 23 51 20 12 9
Completed 46 17 43 19 8 0
Not Completed 7 6 8 1 4 9
Reason Not Completed
Lack of Efficacy             4             4             5             1             4             7
Adverse Event             2             0             2             0             0             0
Withdrawal by Subject             0             1             1             0             0             0
Death             0             1             0             0             0             0
Poor compliance/noncompliance             1             0             0             0             0             0
Administrative reason by sponsor             0             0             0             0             0             1
Completed 12 Week only             0             0             0             0             0             1
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null) Total
Hide Arm/Group Description Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period. Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up. Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up. Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period. Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks. Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 53 23 51 20 12 9 168
Hide Baseline Analysis Population Description
The analysis was performed on the treated participants defined as all randomized participants who received at least 1 dose of active study therapy.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 23 participants 51 participants 20 participants 12 participants 9 participants 168 participants
<21 years 0 0 0 1 1 0 2
21-<65 years 41 19 42 11 11 9 133
>=65 years 12 4 9 8 0 0 33
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 23 participants 51 participants 20 participants 12 participants 9 participants 168 participants
Female
31
  58.5%
11
  47.8%
26
  51.0%
11
  55.0%
5
  41.7%
2
  22.2%
86
  51.2%
Male
22
  41.5%
12
  52.2%
25
  49.0%
9
  45.0%
7
  58.3%
7
  77.8%
82
  48.8%
Hepatitis C Virus RNA Distribution  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 23 participants 51 participants 20 participants 12 participants 9 participants 168 participants
<800,000 IU/mL 12 3 11 4 5 0 35
≥800,000 IU/mL 41 20 40 16 7 9 133
Randomization Stratum  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 23 participants 51 participants 20 participants 12 participants 9 participants 168 participants
Hepatitis C Virus Genotype 1b 53 23 51 20 0 0 147
Hepatitis C Virus Genotype 1a 0 0 0 0 12 9 21
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)
Hide Description SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Post Treatment Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized and received at least 1 dose of active study therapy (daclatasvir, simeprevir, ribavirin).
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
84.9
(78.6 to 91.2)
69.6
(57.3 to 81.9)
74.5
(66.7 to 82.3)
95
(88.8 to 100)
66.7
(49.2 to 84.1)
0 [1] 
(NA to NA)
[1]
As none of the participants responded to SVR12, 80% confidence interval value is not available.
2.Secondary Outcome
Title Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
Hide Description RVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
79.2
(72.1 to 86.4)
69.6
(57.3 to 81.9)
68.6
(60.3 to 77.0)
85
(74.8 to 95.2)
75
(59.0 to 91.0)
33.3
(13.2 to 53.5)
3.Secondary Outcome
Title Percentage of Participants With Complete Early Virologic Response (cEVR)
Hide Description cEVR was defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
84.9
(78.6 to 91.2)
73.9
(62.2 to 85.6)
82.4
(75.5 to 89.2)
90
(81.4 to 98.6)
66.7
(49.2 to 84.1)
11.1
(0 to 24.5)
4.Secondary Outcome
Title Percentage of Participants With Extended Rapid Virologic Response (eRVR)
Hide Description eRVR were defined as hepatitis C virus (HCV) RNA levels to be <lower limit of quantitation, target not detected at both Week 4 and Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Week 4 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
71.7
(63.8 to 79.6)
60.9
(47.8 to 73.9)
62.7
(54.1 to 71.4)
75
(62.6 to 87.4)
58.3
(40.1 to 76.6)
11.1
(0 to 24.5)
5.Secondary Outcome
Title Percentage of Participants With End of Treatment Response (EOTR)
Hide Description EOTR were defined as hepatitis C virus (HCV) RNA levels <lower limit of quantitation, target not detected at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame End of treatment (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: Percentage of participants
88.7
(83.1 to 94.3)
78.3
(67.2 to 89.3)
78.4
(71.1 to 85.8)
95
(88.8 to 100)
66.7
(49.2 to 84.1)
0 [1] 
(NA to NA)
[1]
As none of the participants responded at EOT, hence 80% confidence interval value is not available.
6.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories
Hide Description Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Time Frame Baseline, post-treatment Week 12 (Follow-up period)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants. Here ‘n’ signifies those participants evaluable for this measure at specified time points for each group, respectively.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive) Genotype 1b: Daclatasvir + Simeprevir (Null) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1b: Daclatasvir + Simeprevir + Ribavirin (Null) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Naive) Genotype 1a: Daclatasvir + Simeprevir + Ribavirin (Null)
Hide Arm/Group Description:
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with hepatitis C virus genotype 1b, and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal QD, for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with no prior treatment of hepatitis C virus genotype 1b. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with hepatitis C virus genotype 1b, who never attained ≥2 log10 decline in hepatitis C virus RNA level after 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID were continued to receive treatment for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up period.
Participants with no prior treatment of hepatitis C virus genotype 1a. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Participants with hepatitis C virus genotype 1a, who never attained ≥2 log10 decline in hepatitis C virus genotype RNA level after 12 weeks of prior therapy. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 53 23 51 20 12 9
Measure Type: Number
Unit of Measure: Percentage of participants
IL28B Genotype CC type (n= 16,1,13,1,3,0) 87.5 100 84.6 100 66.7 NA [1] 
IL28B Genotype CT type (n= 22,15, 28,10,9,8) 95.5 60 82.1 90 66.7 0
IL28B Genotype TT type (n= 12,6,10,7,0,1) 66.7 83.3 40 100 NA [2]  0
[1]
As no participant was evaluable for assessment, hence value is not available.
[2]
No participants were available for assessment
7.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
Hide Description 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 with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants.
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) Genotype1a: Daclatasvir +Simeprevir + Ribavirin(Naive + Null)
Hide Arm/Group Description:
Participants with and without prior treatment of hepatitis C virus genotype 1b and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period.
Participants with and without prior treatment of hepatitis C virus genotype 1b and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up.
Participants with and without prior treatment of hepatitis C virus genotype 1a and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
Overall Number of Participants Analyzed 76 71 21
Measure Type: Number
Unit of Measure: Participants
SAEs 7 3 1
AEs Leading to Discontinuation 2 2 0
Death 1 0 0
Time Frame From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)
Adverse Event Reporting Description On-Treatment Period
 
Arm/Group Title Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) Genotype1a: Daclatasvir +Simeprevir + Ribavirin (Naive + Null)
Hide Arm/Group Description Participants with and without prior treatment of hepatitis C virus genotype 1b and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food and simeprevir 150 mg with a light to standard meal once daily (QD), for a period of 12 weeks or 24 weeks based on re-randomization and continued into a post-treatment follow-up period. Participants with and without prior treatment of hepatitis C virus genotype 1b and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>= 75 kg, respectively) ribavirin twice daily (BID) for a period of 12 or 24 weeks based on re-randomization and continued into post-treatment follow-up. Participants with and without prior treatment of hepatitis C virus genotype 1a and who never attained ≥2 log10 decline in hepatitis C virus RNA levels after at least 12 weeks of prior therapy with peginterferon/ribavirin. Received daclatasvir 30 mg with or without food, simeprevir 150 mg with a light to standard meal QD, and weight stratified (1000/1200 mg for participants weighing <75/>=75 kg, respectively) ribavirin BID for a period of 24 weeks and continued into post-treatment follow-up period of 24 weeks.
All-Cause Mortality
Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) Genotype1a: Daclatasvir +Simeprevir + Ribavirin (Naive + Null)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) Genotype1a: Daclatasvir +Simeprevir + Ribavirin (Naive + Null)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/76 (9.21%)   3/71 (4.23%)   1/21 (4.76%) 
Gastrointestinal disorders       
Constipation  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Hepatobiliary disorders       
Liver disorder  1  0/76 (0.00%)  1/71 (1.41%)  0/21 (0.00%) 
Infections and infestations       
Pneumonia  1  1/76 (1.32%)  1/71 (1.41%)  0/21 (0.00%) 
Injury, poisoning and procedural complications       
Post lumbar puncture syndrome  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Hepatic cancer  1  0/76 (0.00%)  0/71 (0.00%)  1/21 (4.76%) 
Nervous system disorders       
Intracranial haematoma  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Hypoaesthesia  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Ischaemic stroke  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Neurotoxicity  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Psychiatric disorders       
Depression  1  1/76 (1.32%)  0/71 (0.00%)  0/21 (0.00%) 
Vascular disorders       
Thrombophlebitis superficial  1  0/76 (0.00%)  1/71 (1.41%)  0/21 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Genotype 1b: Daclatasvir + Simeprevir (Naive + Null) Genotype1b: Daclatasvir +Simeprevir + Ribavirin (Naive + Null) Genotype1a: Daclatasvir +Simeprevir + Ribavirin (Naive + Null)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/76 (64.47%)   63/71 (88.73%)   21/21 (100.00%) 
Blood and lymphatic system disorders       
Anaemia  1  1/76 (1.32%)  12/71 (16.90%)  1/21 (4.76%) 
Eye disorders       
Dry eye  1  1/76 (1.32%)  1/71 (1.41%)  2/21 (9.52%) 
Visual acuity reduced  1  0/76 (0.00%)  0/71 (0.00%)  2/21 (9.52%) 
Gastrointestinal disorders       
Abdominal distension  1  4/76 (5.26%)  0/71 (0.00%)  2/21 (9.52%) 
Abdominal pain  1  4/76 (5.26%)  2/71 (2.82%)  5/21 (23.81%) 
Nausea  1  14/76 (18.42%)  11/71 (15.49%)  4/21 (19.05%) 
Gastric disorder  1  0/76 (0.00%)  0/71 (0.00%)  2/21 (9.52%) 
Dyspepsia  1  2/76 (2.63%)  5/71 (7.04%)  0/21 (0.00%) 
Gastrooesophageal reflux disease  1  3/76 (3.95%)  4/71 (5.63%)  0/21 (0.00%) 
Abdominal pain upper  1  3/76 (3.95%)  5/71 (7.04%)  0/21 (0.00%) 
Constipation  1  6/76 (7.89%)  5/71 (7.04%)  4/21 (19.05%) 
Diarrhoea  1  5/76 (6.58%)  2/71 (2.82%)  2/21 (9.52%) 
Vomiting  1  0/76 (0.00%)  3/71 (4.23%)  2/21 (9.52%) 
General disorders       
Irritability  1  3/76 (3.95%)  1/71 (1.41%)  2/21 (9.52%) 
Fatigue  1  6/76 (7.89%)  11/71 (15.49%)  7/21 (33.33%) 
Asthenia  1  15/76 (19.74%)  16/71 (22.54%)  5/21 (23.81%) 
Influenza like illness  1  5/76 (6.58%)  1/71 (1.41%)  3/21 (14.29%) 
Chills  1  1/76 (1.32%)  2/71 (2.82%)  2/21 (9.52%) 
Pain  1  3/76 (3.95%)  1/71 (1.41%)  2/21 (9.52%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  1/76 (1.32%)  12/71 (16.90%)  3/21 (14.29%) 
Jaundice  1  1/76 (1.32%)  4/71 (5.63%)  0/21 (0.00%) 
Infections and infestations       
Nasopharyngitis  1  10/76 (13.16%)  9/71 (12.68%)  2/21 (9.52%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/76 (3.95%)  1/71 (1.41%)  4/21 (19.05%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  3/76 (3.95%)  1/71 (1.41%)  2/21 (9.52%) 
Back pain  1  4/76 (5.26%)  0/71 (0.00%)  1/21 (4.76%) 
Nervous system disorders       
Headache  1  16/76 (21.05%)  10/71 (14.08%)  6/21 (28.57%) 
Disturbance in attention  1  2/76 (2.63%)  0/71 (0.00%)  2/21 (9.52%) 
Paraesthesia  1  2/76 (2.63%)  2/71 (2.82%)  3/21 (14.29%) 
Psychiatric disorders       
Sleep disorder  1  5/76 (6.58%)  5/71 (7.04%)  3/21 (14.29%) 
Depressed mood  1  0/76 (0.00%)  0/71 (0.00%)  2/21 (9.52%) 
Insomnia  1  4/76 (5.26%)  7/71 (9.86%)  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  4/76 (5.26%)  11/71 (15.49%)  2/21 (9.52%) 
Cough  1  2/76 (2.63%)  7/71 (9.86%)  4/21 (19.05%) 
Skin and subcutaneous tissue disorders       
Dry skin  1  5/76 (6.58%)  5/71 (7.04%)  4/21 (19.05%) 
Alopecia  1  3/76 (3.95%)  4/71 (5.63%)  0/21 (0.00%) 
Eczema  1  0/76 (0.00%)  2/71 (2.82%)  2/21 (9.52%) 
Pruritus  1  5/76 (6.58%)  15/71 (21.13%)  5/21 (23.81%) 
Photosensitivity reaction  1  6/76 (7.89%)  3/71 (4.23%)  1/21 (4.76%) 
Rash  1  3/76 (3.95%)  9/71 (12.68%)  3/21 (14.29%) 
Vascular disorders       
Hot flush  1  0/76 (0.00%)  1/71 (1.41%)  2/21 (9.52%) 
Hypertension  1  5/76 (6.58%)  2/71 (2.82%)  1/21 (4.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01628692    
Other Study ID Numbers: AI444-062
2012-000070-28 ( EudraCT Number )
First Submitted: June 25, 2012
First Posted: June 27, 2012
Results First Submitted: August 13, 2015
Results First Posted: November 30, 2015
Last Update Posted: February 23, 2017