Sofosbuvir in Combination With Pegylated Interferon and Ribavirin and in Treatment-Naive Hepatitis C-infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01188772
First received: August 23, 2010
Last updated: April 2, 2014
Last verified: April 2014
Results First Received: January 6, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hepatitis C Virus
Interventions: Drug: Sofosbuvir
Drug: Placebo to match sofosbuvir
Drug: PEG
Drug: RBV

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled in a total of 22 study sites in the United States. The first participant was screened on 16 August 2010. The last participant observation was on 11 May 2012.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
147 participants were randomized, and 146 participants received at least one dose of study drug, and comprise the Safety Analysis Set.

Reporting Groups
  Description
Sofosbuvir 200 mg (Genotype 1) Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 200 mg (2 x 100 mg tablets)+placebo to match sofosbuvir (2 tablets)+pegylated interferon alfa-2a (PEG)+ribavirin (RBV) for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Sofosbuvir 400 mg (Genotype 1) Participants with genotype 1 HCV infection were randomized to receive sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Placebo (Genotype 1) Participants with genotype 1 HCV infection were randomized to receive placebo to match sofosbuvir (4 tablets)+PEG+RBV for 12 weeks followed by PEG+RBV for up to an additional 36 weeks.
Sofosbuvir 400 mg (Genotype 2/3) Participants with genotype 2 or 3 HCV infection received sofosbuvir 400 mg (4 x 100 mg tablets)+PEG+RBV for 12 weeks.

Participant Flow:   Overall Study
    Sofosbuvir 200 mg (Genotype 1)     Sofosbuvir 400 mg (Genotype 1)     Placebo (Genotype 1)     Sofosbuvir 400 mg (Genotype 2/3)  
STARTED     48     48     26     25  
Randomized and Treated     48     47     26     25  
COMPLETED     43     45     15     24  
NOT COMPLETED     5     3     11     1  
Randomized but Not Treated                 0                 1                 0                 0  
Adverse Event                 0                 1                 2                 0  
Lost to Follow-up                 4                 1                 1                 1  
Non-responder                 0                 0                 3                 0  
Physician Decision                 0                 0                 1                 0  
Terminated by Sponsor                 0                 0                 1                 0  
Treatment Failure                 0                 0                 1                 0  
Virologic Failure                 1                 0                 0                 0  
Withdrawal by Subject                 0                 0                 2                 0  



  Baseline Characteristics
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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 at least one dose of study drug

Reporting Groups
  Description
Sofosbuvir 200 mg (Genotype 1) Sofosbuvir 200 mg+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks
Sofosbuvir 400 mg (Genotype 1) Sofosbuvir 400 mg+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks
Placebo (Genotype 1) Placebo to match sofosbuvir+PEG+RBV for 12 weeks; PEG+RBV for up to an additional 36 weeks
Sofosbuvir 400 mg (Genotype 2/3) Sofosbuvir 400 mg+PEG+RBV for 12 weeks
Total Total of all reporting groups

Baseline Measures
    Sofosbuvir 200 mg (Genotype 1)     Sofosbuvir 400 mg (Genotype 1)     Placebo (Genotype 1)     Sofosbuvir 400 mg (Genotype 2/3)     Total  
Number of Participants  
[units: participants]
  48     47     26     25     146  
Age  
[units: years]
Mean ± Standard Deviation
  48.4  ± 11.49     51.4  ± 9.37     48.6  ± 9.35     47.2  ± 11.07     49.2  ± 10.41  
Gender  
[units: participants]
         
Female     15     26     7     9     57  
Male     33     21     19     16     89  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     5     6     1     8     20  
Not Hispanic or Latino     43     41     24     17     125  
Unknown or Not Reported     0     0     1     0     1  
Race/Ethnicity, Customized  
[units: participants]
         
American Indian or Alaska native     0     1     0     0     1  
Asian     1     0     0     0     1  
Black or African American     6     7     5     4     22  
Other     2     2     0     1     5  
White     39     37     21     20     117  
Hepatitis C (HCV) RNA  
[units: log10┬áIU/mL]
Mean ± Standard Deviation
  6.54  ± 0.630     6.39  ± 0.827     6.50  ± 0.762     6.07  ± 0.794     6.40  ± 0.760  
Liver Biopsy Fibrosis Score  
[units: participants]
         
None or Minimal Fibrosis     12     7     3     7     29  
Portal Fibrosis     35     38     21     18     112  
Bridging Fibrosis     1     2     2     0     5  
Cirrhosis     0     0     0     0     0  
Alanine Aminotransferase (ALT)  
[units: IU/L]
Mean ± Standard Deviation
  81.9  ± 66.07     76.1  ± 67.56     81.4  ± 49.14     74.5  ± 54.81     78.7  ± 61.53  
IL28b Genotype [1]
[units: participants]
         
CC     21     18     11     7     57  
CT     24     19     11     17     71  
TT     3     10     4     1     18  
[1] CC, CT, and TT alleles are different forms of the IL28b gene.



  Outcome Measures
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1.  Primary:   Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period   [ Time Frame: Baseline to Week 12 plus 30 days ]

2.  Secondary:   Change in HCV RNA From Baseline to Week 12   [ Time Frame: Baseline to Week 12 ]

3.  Secondary:   Percentage of Participants With Rapid Virologic Response at Week 4   [ Time Frame: Week 4 ]

4.  Secondary:   Percentage of Participants With Complete Early Virologic Response at Week 12   [ Time Frame: Week 12 ]

5.  Secondary:   Percentage of Participants With Extended Rapid Virologic Response   [ Time Frame: Week 4 to Week 12 ]

6.  Secondary:   Percentage of Participants With Virologic Response at the End of Treatment   [ Time Frame: Week 48 (genotype 1) or Week 12 (genotype 2/3) ]

7.  Secondary:   Percentage of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12) and 24 (SVR24)   [ Time Frame: Post-treatment Weeks 12 and 24 ]

8.  Secondary:   Plasma Pharmacokinetics of GS-331007 (Cmax at Day 8)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

9.  Secondary:   Plasma Pharmacokinetics of GS-331007 (Cmax at Day 15)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

10.  Secondary:   Plasma Pharmacokinetics of GS-331007 (Cmax at Day 29)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

11.  Secondary:   Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 8)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

12.  Secondary:   Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 15)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

13.  Secondary:   Plasma Pharmacokinetics of GS-331007 (AUCtau at Day 29)   [ Time Frame: 1, 2, 4, 8, and 12 hours postdose ]

14.  Secondary:   Percentage of Participants Who Developed Resistance to Sofosbuvir   [ Time Frame: Baseline to Week 12 ]


  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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  More Information
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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: NCT01188772     History of Changes
Other Study ID Numbers: P7977-0422
Study First Received: August 23, 2010
Results First Received: January 6, 2014
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration