Trial Outcomes & Findings for Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant (NCT NCT01559844)
NCT ID: NCT01559844
Last Updated: 2016-07-27
Results Overview
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
61 participants
Primary outcome timeframe
Posttransplant Week 12
Results posted on
2016-07-27
Participant Flow
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.
92 participants were screened.
Participant milestones
| Measure |
SOF+RBV
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.
|
|---|---|
|
Overall Study
STARTED
|
61
|
|
Overall Study
COMPLETED
|
36
|
|
Overall Study
NOT COMPLETED
|
25
|
Reasons for withdrawal
| Measure |
SOF+RBV
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.
|
|---|---|
|
Overall Study
Consent Withdrawn
|
7
|
|
Overall Study
Death
|
5
|
|
Overall Study
Efficacy Failure
|
10
|
|
Overall Study
No Longer A Transplant Candidate
|
3
|
Baseline Characteristics
Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
Baseline characteristics by cohort
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 5.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
49 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
55 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
55 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
5 participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
1 participants
n=5 Participants
|
|
Prior Hepatitis C Virus (HCV) Treatment
Yes
|
46 participants
n=5 Participants
|
|
Prior Hepatitis C Virus (HCV) Treatment
No
|
15 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Non-Responder: Null
|
11 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Non-Responder: Partial
|
11 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Responder: Breakthrough
|
3 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Responder: Relapser
|
9 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Unknown
|
12 participants
n=5 Participants
|
|
Response to Last Prior HCV Treatment Regimen
Had Not Received Prior Treatment
|
15 participants
n=5 Participants
|
|
Days on Transplant Waitlist
|
266 days
STANDARD_DEVIATION 488.8 • n=5 Participants
|
|
Baseline HCV RNA
|
6.14 log10 IU/mL
STANDARD_DEVIATION 0.633 • n=5 Participants
|
|
Baseline HCV RNA Category
< 6 log10 IU/mL
|
20 participants
n=5 Participants
|
|
Baseline HCV RNA Category
≥ 6 and < 7 log10 IU/mL
|
38 participants
n=5 Participants
|
|
Baseline HCV RNA Category
≥ 7 log10 IU/mL
|
3 participants
n=5 Participants
|
|
HCV Genotype
Genotype 1a
|
24 participants
n=5 Participants
|
|
HCV Genotype
Genotype 1b
|
21 participants
n=5 Participants
|
|
HCV Genotype
Genotype 2a
|
1 participants
n=5 Participants
|
|
HCV Genotype
Genotype 2b
|
7 participants
n=5 Participants
|
|
HCV Genotype
Genotype 3a
|
7 participants
n=5 Participants
|
|
HCV Genotype
Genotype 4a
|
1 participants
n=5 Participants
|
|
IL28b Status
CC
|
13 participants
n=5 Participants
|
|
IL28b Status
CT
|
39 participants
n=5 Participants
|
|
IL28b Status
TT
|
8 participants
n=5 Participants
|
|
IL28b Status
Missing
|
1 participants
n=5 Participants
|
|
Baseline Child-Pugh Turcotte (CPT) Score
5
|
26 participants
n=5 Participants
|
|
Baseline Child-Pugh Turcotte (CPT) Score
6
|
18 participants
n=5 Participants
|
|
Baseline Child-Pugh Turcotte (CPT) Score
7
|
14 participants
n=5 Participants
|
|
Baseline Child-Pugh Turcotte (CPT) Score
8
|
3 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
6
|
5 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
7
|
18 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
8
|
12 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
9
|
9 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
10
|
6 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
11
|
8 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
13
|
2 participants
n=5 Participants
|
|
Baseline Model For End-Stage Liver Disease (MELD) Score
14
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Posttransplant Week 12Population: 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.
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Outcome measures
| Measure |
SOF+RBV
n=43 Participants
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.
|
|---|---|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Transplant after ≥ 12 weeks of treatment (N=32)
|
75.0 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Transplant after any duration of treatment (N=43)
|
69.8 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 48 weeks prior to transplantPopulation: Safety Analysis Set
Outcome measures
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
|
3.3 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 48 weeks following transplantPopulation: Participants in the Safety Analysis Set who underwent liver transplantation were analyzed.
Outcome measures
| Measure |
SOF+RBV
n=46 Participants
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.
|
|---|---|
|
Percentage of Participants With Graft Loss Following Transplant
|
6.5 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 48 weeks following transplantPopulation: Safety Analysis Set
* 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.
Outcome measures
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
Number of Participants Who Died
All Deaths
|
5 participants
|
|
Number of Participants Who Died
Treatment-Emergent Death (N = 61)
|
1 participants
|
|
Number of Participants Who Died
Death Following Transplant (N = 46)
|
3 participants
|
|
Number of Participants Who Died
Death Not Meeting Either Criteria (N = 61)
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks following transplantPopulation: 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.
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at the relevant time point after transplant.
Outcome measures
| Measure |
SOF+RBV
n=32 Participants
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.
|
|---|---|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 1 (N = 32)
|
87.5 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 2 (N = 32)
|
81.3 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 4 (N = 32)
|
75.0 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 8 (N = 32)
|
75.0 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 24 (N = 32)
|
75.0 percentage of participants
|
|
Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48
Posttransplant Week 48 (N = 30)
|
66.7 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 48 weeks prior to transplantPopulation: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 48 (N = 8)
|
100.0 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 1 (N = 61)
|
13.1 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 2 (N = 61)
|
57.4 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 3 (N = 60)
|
81.7 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 4 (N = 58)
|
93.1 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 8 (N = 54)
|
90.7 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 12 (N = 48)
|
93.8 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 24 (N = 30)
|
100.0 percentage of participants
|
|
Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48
Week 36 (N = 9)
|
100.0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 8 weeks prior to transplantPopulation: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Week 1 (N = 59)
|
-3.87 log10 IU/mL
Standard Deviation 0.700
|
|
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Week 2 (N = 61)
|
-4.43 log10 IU/mL
Standard Deviation 0.771
|
|
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Week 3 (N = 60)
|
-4.64 log10 IU/mL
Standard Deviation 0.670
|
|
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Week 4 (N = 58)
|
-4.69 log10 IU/mL
Standard Deviation 0.686
|
|
HCV RNA and Change From Baseline in HCV RNA Through Week 8
Week 8 (N = 53)
|
-4.66 log10 IU/mL
Standard Deviation 0.708
|
SECONDARY outcome
Timeframe: Up to 48 weeks prior to transplantPopulation: 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.
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)
Outcome measures
| Measure |
SOF+RBV
n=61 Participants
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.
|
|---|---|
|
Proportion of Participants With Virologic Failure Prior to Transplant
On-treatment VF (N = 61)
|
8.2 percentage of participants
|
|
Proportion of Participants With Virologic Failure Prior to Transplant
Posttreatment/Pretransplant VF - 24 Weeks (N = 15)
|
73.3 percentage of participants
|
|
Proportion of Participants With Virologic Failure Prior to Transplant
Posttreatment/Pretransplant VF - 48 Weeks (N = 8)
|
37.5 percentage of participants
|
Adverse Events
SOF+RBV
Serious events: 11 serious events
Other events: 49 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SOF+RBV
n=61 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal strangulated hernia
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Mesenteric artery thrombosis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Umbilical hernia, obstructive
|
3.3%
2/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Pyrexia
|
3.3%
2/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Cellulitis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Infectious pleural effusion
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Peritonitis bacterial
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Sepsis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
3.3%
2/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour thrombosis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Hepatic encephalopathy
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Confusional state
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Renal and urinary disorders
Renal failure acute
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.6%
1/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
Other adverse events
| Measure |
SOF+RBV
n=61 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
21.3%
13/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Constipation
|
9.8%
6/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
16.4%
10/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Fatigue
|
37.7%
23/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Oedema peripheral
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Dizziness
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
23.0%
14/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
11.5%
7/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.5%
7/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
11.5%
7/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.6%
4/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.8%
6/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.8%
9/61 • Up to 48 weeks plus 30 days
Safety Analysis Set
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER