Trial Outcomes & Findings for Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation (NCT NCT01687257)

Last Updated: 2016-09-16

Results Overview

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. For the Observation/SOF+RBV group, SVR12 during the observational period was defined as HCV RNA \< LLOQ for 12 consecutive weeks, any time during the observational period.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)

Results posted on

2016-09-16

Participant Flow

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 occurred on 06 October 2015.

63 participants were screened.

Participant milestones

Participant milestones
Measure	SOF+RBV (Group 1) Sofosbuvir (Sovaldi®; SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for up to 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 up to 48 weeks.
Overall Study STARTED	25	4	21
Overall Study COMPLETED	17	0	15
Overall Study NOT COMPLETED	8	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	SOF+RBV (Group 1) Sofosbuvir (Sovaldi®; SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for up to 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 up to 48 weeks.
Overall Study Efficacy Failure	6	0	5
Overall Study Subject Withdrew Consent	1	1	1
Overall Study Adverse Event	1	0	0
Overall Study Investigator's Discretion	0	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SOF+RBV (Group 1) n=25 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	SOF+RBV (Group 2; Received Treatment) n=21 Participants 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 up to 48 weeks.	Total n=46 Participants Total of all reporting groups
Age, Continuous	55 years STANDARD_DEVIATION 7.2 • n=5 Participants	56 years STANDARD_DEVIATION 7.0 • n=7 Participants	55 years STANDARD_DEVIATION 7.0 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	22 participants n=5 Participants	20 participants n=7 Participants	42 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment New Zealand	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	12 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment France	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Australia	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Spain	8 participants n=5 Participants	3 participants n=7 Participants	11 participants n=5 Participants
HCV Genotype Genotype 1a	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
HCV Genotype Genotype 1b	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
HCV Genotype Genotype 2a/2c	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
HCV Genotype Genotype 2b	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
HCV Genotype Genotype 3a	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
HCV Genotype Genotype 4	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
HCV Genotype Genotype 4h	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
IL28b Status CC	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
IL28b Status CT	14 participants n=5 Participants	10 participants n=7 Participants	24 participants n=5 Participants
IL28b Status TT	8 participants n=5 Participants	5 participants n=7 Participants	13 participants n=5 Participants
HCV RNA	6.1 log10 IU/mL STANDARD_DEVIATION 0.49 • n=5 Participants	6.2 log10 IU/mL STANDARD_DEVIATION 0.79 • n=7 Participants	6.1 log10 IU/mL STANDARD_DEVIATION 0.64 • n=5 Participants
HCV RNA Category < 800,000 IU/mL	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
HCV RNA Category ≥ 800,000 IU/mL	15 participants n=5 Participants	16 participants n=7 Participants	31 participants n=5 Participants
Hepatic Venous Pressure Gradient (HVPG)	17.4 mmHg STANDARD_DEVIATION 4.70 • n=5 Participants	16.4 mmHg STANDARD_DEVIATION 4.88 • n=7 Participants	17.0 mmHg STANDARD_DEVIATION 4.85 • n=5 Participants
Child-Pugh-Turcotte (CPT) Score Category CPT A (5-6)	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Child-Pugh-Turcotte (CPT) Score Category CPT B (7-10)	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 6	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 7	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 8	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 9	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 10	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 11	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 12	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 13	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 15	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Model for End-Stage Liver Disease (MELD) Score 16	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)

Population: Participants who were randomized to the study.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=25 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=25 Participants 24 weeks of observation	SOF+RBV (Group 2) n=21 Participants Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	72.0 percentage of participants	0 percentage of participants	71.4 percentage of participants	—

SECONDARY outcome

Timeframe: Posttreatment Weeks 4, 24, and 48

Population: Participants who were randomized and received at least 1 dose of study drug with available data were analyzed.

SVR4, SVR24, and SVR48 were defined as HCV RNA \< LLOQ at 4, 24, and 48 weeks after stopping study treatment, respectively.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=25 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=21 Participants 24 weeks of observation	SOF+RBV (Group 2) Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) SVR4 (Group 1: N = 25; Group 2: N = 21)	72.0 percentage of participants	76.2 percentage of participants	—	—
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) SVR24 (Group 1: N = 25; Group 2: N = 21)	68.0 percentage of participants	71.4 percentage of participants	—	—
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) SVR48 (Group 1: N = 17; Group 2: N = 13)	94.1 percentage of participants	100.0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to 48 weeks

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

On-treatment virologic failure was defined as: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=25 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=21 Participants 24 weeks of observation	SOF+RBV (Group 2) Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Percentage of Participants Experiencing On-Treatment Virologic Failure	8.0 percentage of participants	0 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to Posttreatment Week 24

Population: Participants who were randomized and received at least 1 dose of study drug with available data were analyzed.

Viral relapse was defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=23 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=21 Participants 24 weeks of observation	SOF+RBV (Group 2) Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Percentage of Participants Experiencing Viral Relapse	17.4 percentage of participants	23.8 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)

Population: Participants who were randomized to the study with available data at baseline and end of observation or end of treatment were analyzed.

HVPG closely reflects the degree of portal hypertension in patients with cirrhosis. The end of treatment for the Observation group was defined as the end of the observation period. The treatment period for Group 2 was defined as the end of the observation period to the end of the treatment. Baseline values were the last available values on or prior to first dose date of any study drug.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=19 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=21 Participants 24 weeks of observation	SOF+RBV (Group 2) n=18 Participants Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) n=37 Participants Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment	-1.6 mmHg Standard Deviation 4.90	0.5 mmHg Standard Deviation 2.52	-0.4 mmHg Standard Deviation 2.69	-1.0 mmHg Standard Deviation 3.97

SECONDARY outcome

Timeframe: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)

Population: Participants who were randomized to the study with available data were analyzed.

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. Data are presented as improvement, no change, or worsening in CPT scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups). Improvement in CPT score was defined as having a decrease in CPT score from baseline, no change in CPT score was defined as having no change in CPT score from baseline, and worsening in CPT score was defined as having an increase in CPT score from baseline. Baseline values were the last available values on or prior to first dose date of any study drug.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=23 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=20 Participants 24 weeks of observation	SOF+RBV (Group 2) n=18 Participants Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) n=41 Participants Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Change From Baseline in Child-Pugh-Turcotte (CPT) Score Improvement in CPT Score	65.2 percentage of participants	10.0 percentage of participants	38.9 percentage of participants	53.7 percentage of participants
Change From Baseline in Child-Pugh-Turcotte (CPT) Score No Change in CPT Score	26.1 percentage of participants	75.0 percentage of participants	50.0 percentage of participants	36.6 percentage of participants
Change From Baseline in Child-Pugh-Turcotte (CPT) Score Worsening in CPT Score	8.7 percentage of participants	15.0 percentage of participants	11.1 percentage of participants	9.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)

Population: Participants who were randomized to the study with available data were analyzed.

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. Data are presented as improvement, no change, or worsening in MELD scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups). Improvement in MELD score was defined as having a baseline MELD score of 11-15 or 16-20 that changed to 0-10, or a baseline MELD score of 16-20 that changed to 11-15; no change in MELD score was defined as having no change in score group (0-10, 11-15, or 16-20) from baseline; and worsening in MELD score was defined as having a baseline MELD score of 0-10 that changed to 11-15 or 16-20, or a baseline MELD score of 11-15 that changed to 16-20. Baseline values were the last available values on or prior to first dose date of any study drug.

Outcome measures

Outcome measures
Measure	SOF+RBV (Group 1) n=24 Participants SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period (Group 2) n=20 Participants 24 weeks of observation	SOF+RBV (Group 2) n=17 Participants Participants who completed observation and received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	All SOF+RBV (Groups 1 and 2) n=41 Participants Participants who received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 48 weeks in both Groups 1 and 2
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores Improvement in MELD Score	33.3 percentage of participants	20.0 percentage of participants	5.9 percentage of participants	22.0 percentage of participants
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores No Change in MELD Score	54.2 percentage of participants	75.0 percentage of participants	88.2 percentage of participants	68.3 percentage of participants
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores Worsening in MELD Score	12.5 percentage of participants	5.0 percentage of participants	5.9 percentage of participants	9.8 percentage of participants

Adverse Events

SOF+RBV (Group 1)

Serious events: 4 serious events

Other events: 23 other events

Deaths: 0 deaths

Observation Period Only (Group 2)

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

SOF+RBV Treatment Only (Group 2)

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences

Email: [email protected]

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

Measure	SOF+RBV (Group 1) n=25 participants at risk SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period Only (Group 2) n=25 participants at risk This reporting group includes participants who were randomized to the Observation/SOF+RBV group and received up to 24 weeks of observation.	SOF+RBV Treatment Only (Group 2) n=21 participants at risk 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 up to 48 weeks.
Eye disorders Eye swelling	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Ascites	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Oesophageal varices haemorrhage	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Pyrexia	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Hepatobiliary disorders Cholecystitis	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Hepatobiliary disorders Hepatic failure	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Hepatobiliary disorders Jaundice	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Infections and infestations Bacteraemia	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Investigations Blood bilirubin increased	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Hepatic encephalopathy	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Psychiatric disorders Drug abuse	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Renal and urinary disorders Renal failure	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Erythema	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Rash	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.

Measure	SOF+RBV (Group 1) n=25 participants at risk SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for up to 48 weeks	Observation Period Only (Group 2) n=25 participants at risk This reporting group includes participants who were randomized to the Observation/SOF+RBV group and received up to 24 weeks of observation.	SOF+RBV Treatment Only (Group 2) n=21 participants at risk 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 up to 48 weeks.
Blood and lymphatic system disorders Anaemia	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	23.8% 5/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	19.0% 4/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Abdominal pain upper	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Ascites	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Constipation	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Diarrhoea	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	28.6% 6/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Dyspepsia	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Melaena	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Nausea	36.0% 9/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	28.6% 6/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Gastrointestinal disorders Vomiting	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Asthenia	28.0% 7/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Fatigue	24.0% 6/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	42.9% 9/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Oedema peripheral	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	23.8% 5/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Peripheral swelling	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
General disorders Pyrexia	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	19.0% 4/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Hepatobiliary disorders Hyperbilirubinaemia	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Infections and infestations Gastroenteritis viral	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Infections and infestations Influenza	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Infections and infestations Upper respiratory tract infection	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	19.0% 4/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Infections and infestations Urinary tract infection	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Injury, poisoning and procedural complications Fall	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Musculoskeletal and connective tissue disorders Arthralgia	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Musculoskeletal and connective tissue disorders Back pain	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Disturbance in attention	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Dizziness	16.0% 4/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Encephalopathy	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Headache	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	33.3% 7/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Hepatic encephalopathy	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Memory impairment	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Restless legs syndrome	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Nervous system disorders Syncope	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Psychiatric disorders Anxiety	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Psychiatric disorders Insomnia	24.0% 6/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	33.3% 7/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Respiratory, thoracic and mediastinal disorders Cough	16.0% 4/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Alopecia	8.0% 2/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.8% 1/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Dry skin	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Pruritus	32.0% 8/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	14.3% 3/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Rash	24.0% 6/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	12.0% 3/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	0.00% 0/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	4.0% 1/25 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.	9.5% 2/21 • Up to 48 weeks plus 30 days Adverse event data includes all participants who were randomized to the study.