Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sofosbuvir With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6 (ATOMIC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01329978
First received: March 30, 2011
Last updated: April 24, 2014
Last verified: April 2014
Results First Received: January 6, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Hepatitis C, Chronic
Interventions: Drug: Sofosbuvir
Drug: RBV
Drug: PEG

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled in a total of 42 study sites in the United States. The first participant was screened on 23 March 2011. The last participant observation was on 27 August 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
589 participants were screened and 332 were randomized and treated, and comprise the Safety Analysis Set.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive sofosbuvir (SOF) 400 mg+pegylated interferon alfa-2a (PEG) 180 µg+ribavirin (RBV) 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Participant Flow for 2 periods

Period 1:   Sofosbuvir+PEG+RBV Treatment Period
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
STARTED     52     125     155     0     0  
COMPLETED     48 [1]   112 [1]   150 [2]   0     0  
NOT COMPLETED     4     13     5     0     0  
Adverse Event                 1                 2                 0                 0                 0  
Lost to Follow-up                 2                 8                 2                 0                 0  
Withdrawal by Subject                 1                 1                 3                 0                 0  
Subject Was Incarcerated                 0                 1                 0                 0                 0  
Subject Moved Out of State                 0                 1                 0                 0                 0  
[1] Participants in this group were not re-randomized for further treatment
[2] 150 participants were re-randomized after 12 weeks of treatment.

Period 2:   Rerandomization Treatment Period
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
STARTED     0     0     0     75 [1]   75 [1]
COMPLETED     0     0     0     70     71  
NOT COMPLETED     0     0     0     5     4  
Lost to Follow-up                 0                 0                 0                 5                 3  
Withdrawal by Subject                 0                 0                 0                 0                 1  
[1] This group includes participants rerandomized from the SOF+PEG+RBV 12 week/Rerandomization Group.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: participants who were randomized and received at least 1 dose of study drug

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Total Total of all reporting groups

Baseline Measures
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     Total  
Number of Participants  
[units: participants]
  52     125     155     332  
Age  
[units: years]
Mean ± Standard Deviation
  51  ± 9.8     50  ± 11.0     50  ± 10.8     50  ± 10.7  
Gender  
[units: participants]
       
Female     17     52     49     118  
Male     35     73     106     214  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     10     26     31     67  
Not Hispanic or Latino     42     99     124     265  
Unknown or Not Reported     0     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
       
Black     2     17     16     35  
Not Black     50     108     139     297  
Hepatitis C Virus (HCV) genotype [1]
[units: participants]
       
Genotype 1a     40     85     116     241  
Genotype 1b     12     24     39     75  
Genotype 4     0     11     0     11  
Genotype 6     0     2     0     2  
Genotype 6e     0     2     0     2  
Genotype 6o     0     1     0     1  
HCV RNA  
[units: log10 copies/mL]
Mean ± Standard Deviation
  6.5  ± 0.66     6.3  ± 0.73     6.4  ± 0.79     6.4  ± 0.75  
HCV RNA Category  
[units: participants]
       
< 800,000 IU/mL     7     33     28     68  
> 800,000 IU/mL     45     92     127     264  
Liver Biopsy Fibrosis Score  
[units: participants]
       
Missing     0     1     13     14  
Bridging Fibrosis     7     17     23     47  
None or Minimal Fibrosis     9     14     20     43  
Portal Fibrosis     36     93     99     228  
Alanine Aminotransferase (ALT)  
[units: U/L]
Mean ± Standard Deviation
  80.5  ± 71.61     83.7  ± 77.18     76.4  ± 55.91     79.8  ± 66.98  
ALT Category [2]
[units: participants]
       
≤ 1.5 × the upper limit of the normal range (ULN)     37     87     115     239  
> 1.5 × ULN     15     38     40     93  
IL28b Genotype [3]
[units: participants]
       
CC     13     36     39     88  
CT     33     63     88     184  
TT     6     26     28     60  
[1] There are variations of HCV which are all similar enough to be called HCV, but are distinct enough to be referred to as HCV genotypes 1 (a or b), 2, 3, 4, 5, or 6 (e or o).
[2] The ULN for ALT was 60 IU/mL before March 26, 2012, then 56 IU/mL (males) and 45 IU/mL (females).
[3] CC, CT, and TT alleles are different forms of the IL28b gene.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)   [ Time Frame: Post-treatment Week 24 ]

Measure Type Primary
Measure Title Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)
Measure Description SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.
Time Frame Post-treatment Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set (participants who were randomized and received at least 1 dose of study drug) with genotype 1 and who had available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  52     109     155     75     75  
Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  90.4  
  ( 79.0 to 96.8 )  
  92.7  
  ( 86.0 to 96.8 )  
  91.0  
  ( 85.3 to 95.0 )  
  93.3  
  ( 85.1 to 97.8 )  
  94.7  
  ( 86.9 to 98.5 )  


Statistical Analysis 1 for Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)
Groups [1] SOF+PEG+RBV 12 Weeks vs. SOF+PEG+RBV 24 Weeks
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.77
Difference in proportions [4] -1.4
95% Confidence Interval ( -12.2 to 9.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analyses was stratified by IL28B (CC versus any T allele) and plasma HCV RNA (< 800,000 IU/mL versus ≥ 800,000 IU/mL). Only participants with genotype 1 were included in the comparison due to the fact that participants with genotype 4 and 6 were only enrolled in the SOF+PEG+RBV 24 weeks group.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is based on the Cochran-Mantel-Haenszel (CMH) test stratified by randomization stratification factors.
[4] Other relevant estimation information:
  The difference in proportions and its 95% confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel (MH) proportions.

Statistical Analysis 2 for Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)
Groups [1] SOF+PEG+RBV 12 Weeks vs. SOF+PEG+RBV 12 Week/Rerandomization Group
Method [2] Cochran-Mantel-Haenszel
P Value [3] 0.93
Difference in proportions [4] -0.4
95% Confidence Interval ( -10.8 to 9.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analyses was stratified by IL28B (CC versus any T allele) and plasma HCV RNA (< 800,000 IU/mL versus ≥ 800,000 IU/mL).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  The difference in proportions and its 95% CI were calculated based on stratum-adjusted MH proportions.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The p-value is based on the CMH test stratified by randomization stratification factors.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Percentage of Participants Who Experienced Adverse Events   [ Time Frame: Baseline (Day 1) to post-treatment Day 30 ]

Measure Type Primary
Measure Title Percentage of Participants Who Experienced Adverse Events
Measure Description Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time Frame Baseline (Day 1) to post-treatment Day 30  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  52     125     155     75     75  
Percentage of Participants Who Experienced Adverse Events  
[units: percentage of participants]
         
Any AE     98.1     96.8     98.7     98.7     100.0  
Drug-related AE     96.2     94.4     97.4     98.7     97.3  
Grade 3 or higher AE     15.4     17.6     14.2     14.7     13.3  
AE leading to drug discontinuation     5.8     16.0     4.5     5.3     4.0  
Serious AE     3.8     4.8     2.6     2.7     2.7  

No statistical analysis provided for Percentage of Participants Who Experienced Adverse Events



3.  Secondary:   Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)   [ Time Frame: Post-treatment Week 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
Measure Description SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.
Time Frame Post-treatment Week 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  52     125     155     75     75  
Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  90.4  
  ( 79.0 to 96.8 )  
  92.0  
  ( 85.8 to 96.1 )  
  91.0  
  ( 85.3 to 95.0 )  
  93.3  
  ( 85.1 to 97.8 )  
  94.7  
  ( 86.9 to 98.5 )  

No statistical analysis provided for Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)



4.  Secondary:   Change in HCV RNA at Week 2   [ Time Frame: Baseline (Day 1) to Week 2 ]

Measure Type Secondary
Measure Title Change in HCV RNA at Week 2
Measure Description No text entered.
Time Frame Baseline (Day 1) to Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  49     124     153  
Change in HCV RNA at Week 2  
[units: log10 IU/mL]
Mean ± Standard Deviation
  -5.12  ± 0.660     -5.07  ± 0.701     -5.13  ± 0.768  

No statistical analysis provided for Change in HCV RNA at Week 2



5.  Secondary:   Change in HCV RNA at Week 4   [ Time Frame: Baseline (Day 1) to Week 4 ]

Measure Type Secondary
Measure Title Change in HCV RNA at Week 4
Measure Description No text entered.
Time Frame Baseline (Day 1) to Week 4  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  50     123     152  
Change in HCV RNA at Week 4  
[units: log10 IU/mL]
Mean ± Standard Deviation
  -5.33  ± 0.649     -5.19  ± 0.733     -5.24  ± 0.785  

No statistical analysis provided for Change in HCV RNA at Week 4



6.  Secondary:   Change in HCV RNA at Week 8   [ Time Frame: Baseline (Day 1) to Week 8 ]

Measure Type Secondary
Measure Title Change in HCV RNA at Week 8
Measure Description No text entered.
Time Frame Baseline (Day 1) to Week 8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  48     118     151  
Change in HCV RNA at Week 8  
[units: log10 IU/mL]
Mean ± Standard Deviation
  -5.34  ± 0.635     -5.17  ± 0.740     -5.25  ± 0.789  

No statistical analysis provided for Change in HCV RNA at Week 8



7.  Secondary:   Change in HCV RNA at Week 12   [ Time Frame: Baseline (Day 1) to Week 12 ]

Measure Type Secondary
Measure Title Change in HCV RNA at Week 12
Measure Description No text entered.
Time Frame Baseline (Day 1) to Week 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  47     113     150  
Change in HCV RNA at Week 12  
[units: log10 IU/mL]
Mean ± Standard Deviation
  -5.36  ± 0.616     -5.20  ± 0.719     -5.25  ± 0.791  

No statistical analysis provided for Change in HCV RNA at Week 12



8.  Secondary:   Percentage of Participants With HCV RNA < LOD at Week 2   [ Time Frame: Week 2 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV RNA < LOD at Week 2
Measure Description No text entered.
Time Frame Week 2  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with Available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  51     124     153  
Percentage of Participants With HCV RNA < LOD at Week 2  
[units: percentage of participants]
  68.6     85.5     77.1  

No statistical analysis provided for Percentage of Participants With HCV RNA < LOD at Week 2



9.  Secondary:   Percentage of Participants With HCV RNA Below < LOD at Week 4   [ Time Frame: Week 4 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV RNA Below < LOD at Week 4
Measure Description No text entered.
Time Frame Week 4  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with Available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  50     123     153  
Percentage of Participants With HCV RNA Below < LOD at Week 4  
[units: percentage of participants]
  98.0     100.0     98.7  

No statistical analysis provided for Percentage of Participants With HCV RNA Below < LOD at Week 4



10.  Secondary:   Percentage of Participants With HCV RNA Below < LOD at Week 8   [ Time Frame: Week 8 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV RNA Below < LOD at Week 8
Measure Description No text entered.
Time Frame Week 8  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with Available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  48     118     152  
Percentage of Participants With HCV RNA Below < LOD at Week 8  
[units: percentage of participants]
  100.0     100.0     99.3  

No statistical analysis provided for Percentage of Participants With HCV RNA Below < LOD at Week 8



11.  Secondary:   Percentage of Participants With HCV RNA Below < LOD at Week 12   [ Time Frame: Week 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV RNA Below < LOD at Week 12
Measure Description No text entered.
Time Frame Week 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with Available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  47     113     150  
Percentage of Participants With HCV RNA Below < LOD at Week 12  
[units: percentage of participants]
  100.0     100.0     100.0  

No statistical analysis provided for Percentage of Participants With HCV RNA Below < LOD at Week 12



12.  Secondary:   Percentage of Participants With HCV RNA Below < LOD at Week 24   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Percentage of Participants With HCV RNA Below < LOD at Week 24
Measure Description No text entered.
Time Frame Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with Available data were analyzed. No participants in the SOF+PEG+RBV 12 weeks group were analyzed because they received only 12 weeks of treatment.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  0     100     68     74  
Percentage of Participants With HCV RNA Below < LOD at Week 24  
[units: percentage of participants]
      100.0     100.0     98.6  

No statistical analysis provided for Percentage of Participants With HCV RNA Below < LOD at Week 24



13.  Secondary:   Percentage of Participants With ALT Normalization at Week 12   [ Time Frame: Baseline (Day 1) to Week 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Week 12
Measure Description ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.
Time Frame Baseline (Day 1) to Week 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  23     47     71  
Percentage of Participants With ALT Normalization at Week 12  
[units: percentage of participants]
  78.3     76.6     67.6  

No statistical analysis provided for Percentage of Participants With ALT Normalization at Week 12



14.  Secondary:   Percentage of Participants With ALT Normalization at Week 24   [ Time Frame: Baseline (Day 1) to Week 24 ]

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Week 24
Measure Description ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.
Time Frame Baseline (Day 1) to Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed. No participants in the SOF+PEG+RBV 12 weeks group were analyzed because they received only 12 weeks of treatment.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  0     38     35     30  
Percentage of Participants With ALT Normalization at Week 24  
[units: percentage of participants]
      78.9     94.3     100.0  

No statistical analysis provided for Percentage of Participants With ALT Normalization at Week 24



15.  Secondary:   Percentage of Participants With ALT Normalization at Post-treatment Week 4   [ Time Frame: Baseline (Day 1) to Post-treatment Week 4 ]

Measure Type Secondary
Measure Title Percentage of Participants With ALT Normalization at Post-treatment Week 4
Measure Description ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.
Time Frame Baseline (Day 1) to Post-treatment Week 4  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  19     47     63     36     26  
Percentage of Participants With ALT Normalization at Post-treatment Week 4  
[units: percentage of participants]
  89.5     87.2     95.2     91.7     100.0  

No statistical analysis provided for Percentage of Participants With ALT Normalization at Post-treatment Week 4



16.  Secondary:   Percentage of Participants With Virologic Failure During Treatment   [ Time Frame: Baseline (Day 1) to Week 24 ]

Measure Type Secondary
Measure Title Percentage of Participants With Virologic Failure During Treatment
Measure Description

Virologic failure was defined as either

  • HCV RNA ≥ 15 IU/mL after having previously had HCV RNA < 15 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement (ie, breakthrough);
  • > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement (ie, rebound);or
  • HCV RNA persistently ≥ 15 IU/mL through 8 weeks of treatment (ie, nonresponse)

Baseline was Day 1 for all groups.

Time Frame Baseline (Day 1) to Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  52     125     155     75     75  
Percentage of Participants With Virologic Failure During Treatment  
[units: percentage of participants]
         
Viral breakthrough     0.0     0.0     0.0     0.0     0.0  
Viral rebound     0.0     0.0     0.0     0.0     0.0  
Non-response     0.0     0.0     0.0     0.0     0.0  

No statistical analysis provided for Percentage of Participants With Virologic Failure During Treatment



17.  Secondary:   Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).   [ Time Frame: End of treatment to Post-treatment Week 24 ]

Measure Type Secondary
Measure Title Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).
Measure Description Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.
Time Frame End of treatment to Post-treatment Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants in the Safety Analysis Set with available data were analyzed.

Reporting Groups
  Description
SOF+PEG+RBV 12 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.
SOF+PEG+RBV 24 Weeks Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.
SOF+PEG+RBV 12 Week/Rerandomization Group Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
SOF Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.
SOF+RBV Rerandomization Group This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.

Measured Values
    SOF+PEG+RBV 12 Weeks     SOF+PEG+RBV 24 Weeks     SOF+PEG+RBV 12 Week/Rerandomization Group     SOF Rerandomization Group     SOF+RBV Rerandomization Group  
Number of Participants Analyzed  
[units: participants]
  51     124     153     75     75  
Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).  
[units: percentage of participants]
  5.9     1.6     3.9     2.7     2.7  

No statistical analysis provided for Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


No publications provided by Gilead Sciences

Publications automatically indexed to this study:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01329978     History of Changes
Other Study ID Numbers: P7977-0724
Study First Received: March 30, 2011
Results First Received: January 6, 2014
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration