Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01687257
First received: September 12, 2012
Last updated: January 27, 2016
Last verified: January 2016
Results First Received: January 27, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Hepatitis C
Cirrhosis
Portal Hypertension
With or Without Liver Decompensation
Interventions: Drug: SOF
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
Participants were enrolled at study sites in the United States, Europe, Australia, and New Zealand. The first participant was screened on 27 November 2012. The last study visit for this results posting occurred on 20 April 2015.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
63 participants were screened. Data submitted represent interim analysis performed on data collected by the Primary Completion Date, January 2015, and additional data collected through April 2015. Complete data will be submitted in the October 2016.

Reporting Groups
  Description
SOF+RBV (Group 1) Sofosbuvir (Sovaldi®; SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 48 weeks
Observation/SOF+RBV (Group 2; Not Treated) This reporting group only includes participants who were randomized to the Observation/SOF+RBV group who discontinued study prior to receiving study drug.
Observation/SOF+RBV (Group 2; Received Treatment) This reporting group includes participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks.

Participant Flow:   Overall Study
    SOF+RBV (Group 1)     Observation/SOF+RBV (Group 2; Not Treated)     Observation/SOF+RBV (Group 2; Received Treatment)  
STARTED     25     4     21  
COMPLETED     17     0     1  
NOT COMPLETED     8     4     20  
Efficacy Failure                 6                 0                 5  
Subject Withdrew Consent                 1                 1                 1  
Adverse Event                 1                 1                 0  
Investigator's Discretion                 0                 2                 0  
Still on Study                 0                 0                 14  



  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.
Participants who were randomized and received at least 1 dose of study drug

Reporting Groups
  Description
SOF+RBV (Group 1) SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks
SOF+RBV (Group 2; Received Treatment) This reporting group includes participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks.
Total Total of all reporting groups

Baseline Measures
    SOF+RBV (Group 1)     SOF+RBV (Group 2; Received Treatment)     Total  
Number of Participants  
[units: participants]
  25     21     46  
Age  
[units: years]
Mean (Standard Deviation)
  55  (7.2)     56  (7.0)     55  (7.0)  
Gender  
[units: participants]
     
Female     7     5     12  
Male     18     16     34  
Race/Ethnicity, Customized  
[units: participants]
     
Black or African American     1     1     2  
White     21     20     41  
Asian     1     0     1  
Other     2     0     2  
Region of Enrollment [1]
[units: participants]
     
New Zealand     2     4     6  
United States     10     12     22  
France     2     4     6  
Australia     3     2     5  
Spain     8     3     11  
HCV Genotype  
[units: participants]
     
Genotype 1a     10     8     18  
Genotype 1b     9     5     14  
Genotype 2a/2c     1     0     1  
Genotype 2b     1     1     2  
Genotype 3a     2     6     8  
Genotype 4     1     1     2  
Genotype 4h     1     0     1  
IL28b Status [2]
[units: participants]
     
CC     3     6     9  
CT     14     10     24  
TT     8     5     13  
HCV RNA  
[units: log10 IU/mL]
Mean (Standard Deviation)
  6.1  (0.49)     6.2  (0.79)     6.1  (0.64)  
HCV RNA Category  
[units: participants]
     
< 800,000 IU/mL     10     5     15  
≥ 800,000 IU/mL     15     16     31  
Hepatic Venous Pressure Gradient (HVPG)  
[units: mmHg]
Mean (Standard Deviation)
  17.5  (4.88)     16.4  (4.88)     17.0  (4.85)  
Child-Pugh-Turcotte (CPT) Score Category [3]
[units: participants]
     
CPT A (5-6)     8     10     18  
CPT B (7-10)     17     11     28  
Model for End-Stage Liver Disease (MELD) Score [4]
[units: participants]
     
6     1     2     3  
7     0     3     3  
8     5     2     7  
9     3     1     4  
10     5     4     9  
11     0     4     4  
12     4     1     5  
13     2     1     3  
15     3     3     6  
16     2     0     2  
[1] All randomized participants were analyzed for Region of Enrollment (n = 50).
[2] CC, CT, and TT alleles are different forms of the IL28b gene.
[3] CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
[4] MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)   [ Time Frame: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation) ]

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

3.  Secondary:   Percentage of Participants Experiencing On-Treatment Virologic Failure   [ Time Frame: Up to 24 weeks ]

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

5.  Secondary:   Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment   [ Time Frame: Baseline; Week 24 (Observation) and Week 48 (SOF+RBV) ]

6.  Secondary:   Change From Baseline in Child-Pugh-Turcotte (CPT) Score   [ Time Frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV) ]

7.  Secondary:   Change From Baseline in Model for End Stage Liver Disease (MELD) Scores   [ Time Frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV) ]


  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
There were no limitations affecting the analysis or results.


  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
e-mail: ClinicalTrialDisclosures@gilead.com



Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01687257     History of Changes
Other Study ID Numbers: GS-US-334-0125
2012-002457-29 ( EudraCT Number )
Study First Received: September 12, 2012
Results First Received: January 27, 2016
Last Updated: January 27, 2016
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
New Zealand: Medsafe
Australia: Department of Health and Ageing Therapeutic Goods Administration