Sofosbuvir and Ribavirin in Treatment-Naive and Treatment-Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01682720
First received: September 5, 2012
Last updated: October 8, 2014
Last verified: October 2014
Results First Received: October 2, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Hepatitis C
Interventions: Drug: SOF
Drug: RBV
Drug: Placebo to match SOF
Drug: Placebo to match 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
Participants were enrolled at a total of 77 study sites in Europe. The first participant was screened on 19 September 2012. The last participant observation occurred on 08 January 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
  • 475 participants were screened and 421 were randomized.
  • 419 participants were randomized and received at least 1 dose of study drug (Safety Analysis Set).
  • 334 participants with genotype 2 or 3 hepatitis C virus (HCV) infection were randomized and received at least 1 dose of sofosbuvir (Full Analysis Set).

Reporting Groups
  Description
Placebo 12 Weeks (GT2/3) Placebo to match sofosbuvir (SOF) + placebo to match ribavirin (RBV) for 12 weeks in participants with genotype (GT)2 or 3 HCV infection.
SOF 12 Weeks (GT2) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
SOF 12 Weeks (GT3) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
SOF 24 Weeks (GT3) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.

Participant Flow:   Overall Study
    Placebo 12 Weeks (GT2/3)     SOF 12 Weeks (GT2)     SOF 12 Weeks (GT3)     SOF 24 Weeks (GT3)  
STARTED     85     74     12     250  
Included in Full Analysis Set     0     73     11     250  
COMPLETED     0     69     5     211  
NOT COMPLETED     85     5     7     39  
Randomized but Not Treated                 0                 1                 1                 0  
Terminated by Sponsor                 83                 0                 0                 0  
Efficacy Failure                 0                 3                 3                 30  
Lost to Follow-up                 1                 1                 0                 6  
Subject Withdrew Consent                 0                 0                 2                 2  
Adverse Event                 1                 0                 1                 1  



  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 received at least 1 dose of study drug.

Reporting Groups
  Description
Placebo 12 Weeks (GT2/3) Placebo to match SOF + placebo to match RBV for 12 weeks in participants with genotype 2 or 3 HCV infection.
SOF 12 Weeks (GT2) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 HCV infection.
SOF 12 Weeks (GT3) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection.
SOF 24 Weeks (GT3) SOF 400 mg tablet once daily + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 24 weeks in participants with genotype 3 HCV infection.
Total Total of all reporting groups

Baseline Measures
    Placebo 12 Weeks (GT2/3)     SOF 12 Weeks (GT2)     SOF 12 Weeks (GT3)     SOF 24 Weeks (GT3)     Total  
Number of Participants  
[units: participants]
  85     73     11     250     419  
Age  
[units: years]
Mean ± Standard Deviation
  49  ± 10.5     58  ± 10.1     46  ± 8.8     48  ± 10.1     50  ± 10.8  
Gender  
[units: participants]
         
Female     36     33     5     95     169  
Male     49     40     6     155     250  
Race/Ethnicity, Customized  
[units: participants]
         
Hispanic or Latino     10     6     1     36     53  
Not Hispanic or Latino     71     65     10     203     349  
Not Permitted     4     2     0     11     17  
Race/Ethnicity, Customized  
[units: participants]
         
Black or African American     1     5     0     0     6  
White     81     65     11     236     393  
Asian     3     1     0     9     13  
Not permitted     0     2     0     5     7  
Region of Enrollment  
[units: participants]
         
France     13     15     0     53     81  
Estonia     3     2     4     6     15  
Spain     11     5     1     31     48  
Poland     4     0     0     18     22  
Austria     4     2     0     12     18  
Netherlands     5     6     0     14     25  
Germany     14     8     1     46     69  
United Kingdom     17     3     4     31     55  
Italy     9     25     1     27     62  
Sweden     5     7     0     12     24  
HCV Genotype  
[units: participants]
         
Genotype 2     18     73     0     0     91  
Genotype 3     67     0     11     250     328  
Liver Cirrhosis  
[units: participants]
         
No     68     62     9     190     329  
Yes     17     11     2     60     90  
IL28b Status [1]
[units: participants]
         
CC     22     24     4     86     136  
CT     49     41     4     131     225  
TT     14     8     3     33     58  
HCV RNA  
[units: log10┬áIU/mL]
Mean ± Standard Deviation
  6.5  ± 0.69     6.5  ± 0.70     6.2  ± 0.77     6.3  ± 0.74     6.4  ± 0.72  
HCV RNA Category  
[units: participants]
         
< 6 log10 IU/mL     21     16     4     72     113  
≥ 6 log10 IU/mL     64     57     7     178     306  
Prior HCV Treatment Experience  
[units: participants]
         
Experienced     50     41     9     145     245  
Naive     35     32     2     105     174  
Response to prior HCV treatment [2]
[units: participants]
         
Interferon intolerant     0     3     0     10     13  
Nonresponse     18     10     4     41     73  
Relapse/Breakthrough     32     28     5     94     159  
Interferon Eligibility [3]
[units: participants]
         
Interferon eligible     30     27     2     94     153  
Interferon ineligible     5     5     0     11     21  
[1] CC, CT, and TT alleles are different forms of the IL28b gene.
[2] Only participants who were treatment-experienced at baseline were analyzed.
[3] Only participants who were treatment-naive at baseline were analyzed.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)   [ Time Frame: Posttreatment Week 12 ]

2.  Primary:   Adverse Events Leading to Permanent Discontinuation of Study Drug(s)   [ Time Frame: Up to 24 weeks ]

3.  Secondary:   Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)   [ Time Frame: Posttreatment Weeks 4 and 24 ]

4.  Secondary:   Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse   [ Time Frame: Up to Posttreatment Week 24 ]


  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


Publications of Results:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01682720     History of Changes
Other Study ID Numbers: GS-US-334-0133, 2012-001942-16
Study First Received: September 5, 2012
Results First Received: October 2, 2014
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Austria: Federal Office for Safety in Health Care
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency
Italy: Ethics Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Estonia: The State Agency of Medicine
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)