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Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01559844
Recruitment Status : Completed
First Posted : March 21, 2012
Results First Posted : May 28, 2015
Last Update Posted : July 27, 2016
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hepatitis C
Hepatocellular Carcinoma
Interventions Drug: Sofosbuvir
Drug: Ribavirin
Enrollment 61
Recruitment Details Participants were enrolled at study sites in the United States, Spain, and New Zealand. The first participant was screened on 27 March 2012. The last study visit occurred on 20 October 2014.
Pre-assignment Details 92 participants were screened.
Arm/Group Title SOF+RBV
Hide Arm/Group Description Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Period Title: Overall Study
Started 61
Completed 36
Not Completed 25
Reason Not Completed
Consent Withdrawn             7
Death             5
Efficacy Failure             10
No Longer A Transplant Candidate             3
Arm/Group Title SOF+RBV
Hide Arm/Group Description SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Baseline Participants 61
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants
59  (5.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants
Female
12
  19.7%
Male
49
  80.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants
Hispanic or Latino
12
  19.7%
Not Hispanic or Latino
49
  80.3%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
White 55
Black or African American 6
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
United States 55
Spain 5
New Zealand 1
Prior Hepatitis C Virus (HCV) Treatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
Yes 46
No 15
Response to Last Prior HCV Treatment Regimen  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
Non-Responder: Null 11
Non-Responder: Partial 11
Responder: Breakthrough 3
Responder: Relapser 9
Unknown 12
Had Not Received Prior Treatment 15
Days on Transplant Waitlist  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 61 participants
266  (488.8)
Baseline HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 61 participants
6.14  (0.633)
Baseline HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
< 6 log10 IU/mL 20
≥ 6 and < 7 log10 IU/mL 38
≥ 7 log10 IU/mL 3
HCV Genotype   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
Genotype 1a 24
Genotype 1b 21
Genotype 2a 1
Genotype 2b 7
Genotype 3a 7
Genotype 4a 1
[1]
Measure Description: 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.
IL28b Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
CC 13
CT 39
TT 8
Missing 1
[1]
Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.
Baseline Child-Pugh Turcotte (CPT) Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
5 26
6 18
7 14
8 3
[1]
Measure Description: 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.
Baseline Model For End-Stage Liver Disease (MELD) Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 61 participants
6 5
7 18
8 12
9 9
10 6
11 8
13 2
14 1
[1]
Measure Description: 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.
1.Primary Outcome
Title Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Hide Description pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Time Frame Posttransplant Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (enrolled and received at least 1 dose of study drug) who underwent liver transplantation, and who had HCV RNA < LLOQ at last measurement prior to transplant were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 43
Measure Type: Number
Unit of Measure: percentage of participants
Transplant after ≥ 12 weeks of treatment (N=32) 75.0
Transplant after any duration of treatment (N=43) 69.8
2.Primary Outcome
Title Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Hide Description [Not Specified]
Time Frame Up to 48 weeks prior to transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
3.3
3.Primary Outcome
Title Percentage of Participants With Graft Loss Following Transplant
Hide Description [Not Specified]
Time Frame Up to 48 weeks following transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety Analysis Set who underwent liver transplantation were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 46
Measure Type: Number
Unit of Measure: percentage of participants
6.5
4.Primary Outcome
Title Number of Participants Who Died
Hide Description
  • Treatment-emergent deaths were those that occurred while taking study drug or to the minimum of 1) date of transplantation, 2) retreatment 1st dose date, or 3) last dose date + 30 days.
  • Only those participants who underwent liver transplantation were analyzed for death post-transplantation.
Time Frame Up to 48 weeks following transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: participants
All Deaths 5
Treatment-Emergent Death (N = 61) 1
Death Following Transplant (N = 46) 3
Death Not Meeting Either Criteria (N = 61) 1
5.Secondary Outcome
Title Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Hide Description pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at the relevant time point after transplant.
Time Frame Up to 48 weeks following transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set who underwent liver transplantation and who had ≥ 12 weeks treatment and HCV RNA < LLOQ at last measurement prior to transplant were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 32
Measure Type: Number
Unit of Measure: percentage of participants
Posttransplant Week 1 (N = 32) 87.5
Posttransplant Week 2 (N = 32) 81.3
Posttransplant Week 4 (N = 32) 75.0
Posttransplant Week 8 (N = 32) 75.0
Posttransplant Week 24 (N = 32) 75.0
Posttransplant Week 48 (N = 30) 66.7
6.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Hide Description [Not Specified]
Time Frame Up to 48 weeks prior to transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
Week 1 (N = 61) 13.1
Week 2 (N = 61) 57.4
Week 3 (N = 60) 81.7
Week 4 (N = 58) 93.1
Week 8 (N = 54) 90.7
Week 12 (N = 48) 93.8
Week 24 (N = 30) 100.0
Week 36 (N = 9) 100.0
Week 48 (N = 8) 100.0
7.Secondary Outcome
Title HCV RNA and Change From Baseline in HCV RNA Through Week 8
Hide Description [Not Specified]
Time Frame Up to 8 weeks prior to transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 61
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Week 1 (N = 59) -3.87  (0.700)
Week 2 (N = 61) -4.43  (0.771)
Week 3 (N = 60) -4.64  (0.670)
Week 4 (N = 58) -4.69  (0.686)
Week 8 (N = 53) -4.66  (0.708)
8.Secondary Outcome
Title Proportion of Participants With Virologic Failure Prior to Transplant
Hide Description

Virologic failure (VF) in the pretransplant phase was defined by:

  • Breakthrough (HCV RNA ≥ 25 IU/ml after having previously had HCV RNA < 25 IU/ml, while on treatment)
  • Rebound (breakthrough or > 1 log10 IU/ml increase in HCV RNA from nadir while on treatment)
  • Non-response (HCV RNA ≥ 25 IU/ml through 8 weeks of treatment)
  • Pre-transplant relapse (HCV RNA ≥ 25 IU/ml during the Pre-Transplant off-treatment follow-up period after having achieved HCV RNA < 25 IU/ml at last observed HCV RNA on treatment)
Time Frame Up to 48 weeks prior to transplant
Hide Outcome Measure Data
Hide Analysis Population Description
On-treatment VF: Full Analysis Set. Posttreatment/Pretransplant VF - 24 Weeks or 48 Weeks: Participants who completed 24 or 48 weeks of treatment and had an observed or imputed Week 4 posttreatment follow-up HCV RNA value relapsed during posttreatment follow-up were analyzed.
Arm/Group Title SOF+RBV
Hide Arm/Group Description:
SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: percentage of participants
On-treatment VF (N = 61) 8.2
Posttreatment/Pretransplant VF - 24 Weeks (N = 15) 73.3
Posttreatment/Pretransplant VF - 48 Weeks (N = 8) 37.5
Time Frame Up to 48 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title SOF+RBV
Hide Arm/Group Description SOF 400 mg tablet once daily + RBV tablets (1000-1200 mg daily based on weight) for up to 48 weeks or until time of transplant, whichever occured first.
All-Cause Mortality
SOF+RBV
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
SOF+RBV
Affected / at Risk (%)
Total   11/61 (18.03%) 
Cardiac disorders   
Atrial fibrillation  1  1/61 (1.64%) 
Gastrointestinal disorders   
Abdominal pain  1  1/61 (1.64%) 
Abdominal strangulated hernia  1  1/61 (1.64%) 
Mesenteric artery thrombosis  1  1/61 (1.64%) 
Nausea  1  1/61 (1.64%) 
Umbilical hernia, obstructive  1  2/61 (3.28%) 
Vomiting  1  1/61 (1.64%) 
General disorders   
Pyrexia  1  2/61 (3.28%) 
Infections and infestations   
Cellulitis  1  1/61 (1.64%) 
Infectious pleural effusion  1  1/61 (1.64%) 
Peritonitis bacterial  1  1/61 (1.64%) 
Sepsis  1  1/61 (1.64%) 
Metabolism and nutrition disorders   
Hyponatraemia  1  1/61 (1.64%) 
Musculoskeletal and connective tissue disorders   
Intervertebral disc degeneration  1  1/61 (1.64%) 
Osteoarthritis  1  1/61 (1.64%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Hepatocellular carcinoma  1  2/61 (3.28%) 
Prostate cancer  1  1/61 (1.64%) 
Tumour thrombosis  1  1/61 (1.64%) 
Nervous system disorders   
Hepatic encephalopathy  1  1/61 (1.64%) 
Psychiatric disorders   
Confusional state  1  1/61 (1.64%) 
Renal and urinary disorders   
Renal failure acute  1  1/61 (1.64%) 
Respiratory, thoracic and mediastinal disorders   
Pneumonitis  1  1/61 (1.64%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF+RBV
Affected / at Risk (%)
Total   49/61 (80.33%) 
Blood and lymphatic system disorders   
Anaemia  1  13/61 (21.31%) 
Gastrointestinal disorders   
Constipation  1  6/61 (9.84%) 
Diarrhoea  1  4/61 (6.56%) 
Nausea  1  10/61 (16.39%) 
General disorders   
Fatigue  1  23/61 (37.70%) 
Oedema peripheral  1  4/61 (6.56%) 
Infections and infestations   
Urinary tract infection  1  4/61 (6.56%) 
Metabolism and nutrition disorders   
Decreased appetite  1  4/61 (6.56%) 
Nervous system disorders   
Dizziness  1  4/61 (6.56%) 
Headache  1  14/61 (22.95%) 
Psychiatric disorders   
Insomnia  1  7/61 (11.48%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  7/61 (11.48%) 
Dyspnoea  1  7/61 (11.48%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  4/61 (6.56%) 
Pruritus  1  6/61 (9.84%) 
Rash  1  9/61 (14.75%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
EMail: ClinicalTrialDisclosures@gilead.com
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01559844    
Other Study ID Numbers: P7977-2025
First Submitted: March 5, 2012
First Posted: March 21, 2012
Results First Submitted: May 12, 2015
Results First Posted: May 28, 2015
Last Update Posted: July 27, 2016