Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed-Dose Combination in Subjects With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02201901

Acronym

ASTRAL-4

Enrollment

268

Registered

2014-07-28

Start date

2014-07-31

Completion date

2015-11-30

Last updated

2018-11-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C Virus Infection

Keywords

Sofosbuvir, Velpatasvir, SOF/VEL, GS-5816, Hepatitis C, HCV, Cirrhosis, CPT-B

Brief summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) with and without ribavirin (RBV) for 12 weeks and SOF/VEL FDC for 24 weeks in adults with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) class B cirrhosis.

Interventions

DRUGSOF/VEL

400/100 mg tablets administered orally once daily

DRUGRBV

Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Willing and able to provide written informed consent * HCV RNA \> 10\^4 IU/mL at screening * Chronic HCV infection (≥ 6 months) * Confirmed CPT class B (7-9) at screening

Exclusion criteria

* Current or prior history of solid organ transplantation, significant pulmonary disease, significant cardiac disease, or porphyria * Inability to exclude hepatocellular carcinoma (HCC) by imaging within 6 months of baseline/Day 1 * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) * Screening ECG with clinically significant abnormalities * Prior exposure to SOF or any other nucleotide analogue HCV nonstructural protein 5B (NS5B) inhibitor or any HCV NS5A inhibitor * Laboratory results outside of acceptable ranges at screening

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	Up to 24 weeks plus 30 days	—

Secondary

Measure	Time frame	Description
Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	Posttreatment Weeks 4 and 24	SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	—
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	—
Percentage of Participants With Virologic Failure	Up to Posttreatment Week 24	Virologic failure was defined as * On-treatment virologic failure * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment, * \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, * HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Baseline to Posttreatment Week 24	Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Baseline to Posttreatment Week 24	CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease.

Countries

Puerto Rico, United States

Participant flow

Recruitment details

Participants were enrolled at a total of 47 study sites in the United States. The first participant was screened on 31 July 2014. The last study visit occurred on 25 November 2015.

Pre-assignment details

438 participants were screened.

Participants by arm

Arm	Count
SOF/VEL 12 Weeks (Group 1) SOF/VEL (Sofosbuvir/velpatasvir) (400/100 mg) fixed dose combination (FDC) tablet once daily for 12 weeks	90
SOF/VEL+RBV 12 Weeks (Group 2) SOF/VEL (400/100 mg) FDC tablet + Ribavirin (RBV) tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks	87
SOF/VEL 24 Weeks ((Group 3) SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks	90
Total	267

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	1	0
Overall Study	Death	3	3	3
Overall Study	Lack of Efficacy	7	1	6
Overall Study	Lost to Follow-up	2	3	2
Overall Study	Randomized but never treated	0	1	0
Overall Study	Withdrew Consent	2	0	2

Baseline characteristics

Characteristic	SOF/VEL 24 Weeks ((Group 3)	SOF/VEL 12 Weeks (Group 1)	SOF/VEL+RBV 12 Weeks (Group 2)	Total
Age, Continuous	58 years STANDARD_DEVIATION 5.8	58 years STANDARD_DEVIATION 6.3	58 years STANDARD_DEVIATION 6.9	58 years STANDARD_DEVIATION 6.3
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants	13 Participants	13 Participants	39 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants	77 Participants	74 Participants	228 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
HCV Genotype Genotype 1	71 participants	68 participants	68 participants	207 participants
HCV Genotype Genotype 2	4 participants	4 participants	4 participants	12 participants
HCV Genotype Genotype 3	12 participants	14 participants	13 participants	39 participants
HCV Genotype Genotype 4	2 participants	4 participants	2 participants	8 participants
HCV Genotype Genotype 6	1 participants	0 participants	0 participants	1 participants
HCV RNA	5.9 log 10 IU/mL STANDARD_DEVIATION 0.63	6.0 log 10 IU/mL STANDARD_DEVIATION 0.54	5.8 log 10 IU/mL STANDARD_DEVIATION 0.61	5.9 log 10 IU/mL STANDARD_DEVIATION 0.6
HCV RNA Category < 800,000 IU/mL	45 participants	31 participants	42 participants	118 participants
HCV RNA Category ≥ 800,000 IU/mL	45 participants	59 participants	45 participants	149 participants
IL28B CC	20 participants	20 participants	22 participants	62 participants
IL28B CT	49 participants	51 participants	46 participants	146 participants
IL28B Missing	2 participants	0 participants	0 participants	2 participants
IL28B TT	19 participants	19 participants	19 participants	57 participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Asian	2 participants	3 participants	0 participants	5 participants
Race/Ethnicity, Customized Black or African American	6 participants	6 participants	5 participants	17 participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 participants	0 participants	1 participants	1 participants
Race/Ethnicity, Customized Not Disclosed	1 participants	0 participants	0 participants	1 participants
Race/Ethnicity, Customized Other	0 participants	2 participants	1 participants	3 participants
Race/Ethnicity, Customized White	81 participants	79 participants	79 participants	239 participants
Sex: Female, Male Female	27 Participants	33 Participants	21 Participants	81 Participants
Sex: Female, Male Male	63 Participants	57 Participants	66 Participants	186 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	65 / 90	74 / 87	61 / 90
serious Total, serious adverse events	17 / 90	14 / 87	16 / 90

Outcome results

Primary

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Time frame: Up to 24 weeks plus 30 days

Population: Safety Analysis Set

Arm	Measure	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	1.1 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	16.1 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event	4.4 percentage of participants

Primary

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.

Time frame: Posttreatment Week 12

Population: The Full Analysis Set (FAS): participants who were randomized into the study and received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	83.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	94.3 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	87.8 percentage of participants

Comparison: A sample size of 75 participants per treatment group would provide over 99% power to detect 40% improvement in SVR12 rate from the assumed spontaneous rate of 1% or less using a 2-sided exact 1-sample binomial test at significance level of 0.0167.p-value: <0.001Binomial test

Secondary

Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Time frame: Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Population: Participants in the Full Analysis Set with available data were analyzed.

Arm	Measure	Group	Value (MEAN)	Dispersion
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=89; Group 2: N=83; Group 3: N=88)	-3.51 log10 IU/mL	Standard Deviation 0.652
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	NA log10 IU/mL	—
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	-4.87 log10 IU/mL	Standard Deviation 0.536
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16 (Group 1: N=0; Group 2: N=0; Group 3: N=85)	NA log10 IU/mL	—
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	NA log10 IU/mL	—
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=83; Group 3: N=87)	-4.87 log10 IU/mL	Standard Deviation 0.536
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4(Group 1: N=88; Group 2: N=86; Group 3: N=88)	-4.78 log10 IU/mL	Standard Deviation 0.549
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2(Group 1: N=89; Group 2: N=87; Group 3: N=88)	-4.24 log10 IU/mL	Standard Deviation 0.677
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3, N=87)	-4.87 log10 IU/mL	Standard Deviation 0.536
SOF/VEL 12 Weeks (Group 1)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=82; Group 3: N=86)	-4.87 log10 IU/mL	Standard Deviation 0.536
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3, N=87)	-4.67 log10 IU/mL	Standard Deviation 0.634
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=82; Group 3: N=86)	-4.68 log10 IU/mL	Standard Deviation 0.624
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2(Group 1: N=89; Group 2: N=87; Group 3: N=88)	-4.17 log10 IU/mL	Standard Deviation 0.647
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16 (Group 1: N=0; Group 2: N=0; Group 3: N=85)	NA log10 IU/mL	—
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	NA log10 IU/mL	—
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	NA log10 IU/mL	—
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4(Group 1: N=88; Group 2: N=86; Group 3: N=88)	-4.58 log10 IU/mL	Standard Deviation 0.568
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=89; Group 2: N=83; Group 3: N=88)	-3.63 log10 IU/mL	Standard Deviation 0.691
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	-4.68 log10 IU/mL	Standard Deviation 0.607
SOF/VEL+RBV 12 Weeks (Group 2)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=83; Group 3: N=87)	-4.68 log10 IU/mL	Standard Deviation 0.622
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	-4.77 log10 IU/mL	Standard Deviation 0.613
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16 (Group 1: N=0; Group 2: N=0; Group 3: N=85)	-4.76 log10 IU/mL	Standard Deviation 0.617
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=89; Group 2: N=83; Group 3: N=88)	-3.72 log10 IU/mL	Standard Deviation 0.68
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2(Group 1: N=89; Group 2: N=87; Group 3: N=88)	-4.38 log10 IU/mL	Standard Deviation 0.669
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4(Group 1: N=88; Group 2: N=86; Group 3: N=88)	-4.70 log10 IU/mL	Standard Deviation 0.613
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	-4.74 log10 IU/mL	Standard Deviation 0.63
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=83; Group 3: N=87)	-4.76 log10 IU/mL	Standard Deviation 0.613
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=82; Group 3: N=86)	-4.75 log10 IU/mL	Standard Deviation 0.618
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20 (Group 1: N=0; Group 2: N=0; Group 3: N =84)	-4.77 log10 IU/mL	Standard Deviation 0.613
SOF/VEL 24 Weeks (Group 3)	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3, N=87)	-4.76 log10 IU/mL	Standard Deviation 0.613

Secondary

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score

CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease.

Time frame: Baseline to Posttreatment Week 24

Population: Participants in the Full Analysis Set with available data were analyzed.

Arm	Measure	Group	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	No Change	43.5 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Decrease (Improvement)	44.9 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Increase (Worsening)	11.6 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	No Change	37.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Decrease (Improvement)	53.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Increase (Worsening)	9.3 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Decrease (Improvement)	63.8 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	Increase (Worsening)	8.7 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score	No Change	27.5 percentage of participants

Secondary

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score

Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.

Time frame: Baseline to Posttreatment Week 24

Population: Participants in the Full Analysis Set with available data were analyzed.

Arm	Measure	Group	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	No Change	20.3 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Decrease (Improvement)	55.1 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Increase (Worsening)	24.6 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	No Change	25.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Decrease (Improvement)	49.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Increase (Worsening)	25.3 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Decrease (Improvement)	50.7 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	Increase (Worsening)	27.5 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score	No Change	21.7 percentage of participants

Secondary

Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Time frame: Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Population: Participants in the Full Analysis Set with available data were analyzed.

Arm	Measure	Group	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=90; Group 2: N=87; Group 3: N=90)	2.2 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2 (Group 1: N=90; Group 2: N=87;Group 3: N=89)	34.4 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4 (Group 1: N=90; Group 2: N=87; Group 3: N=89)	81.1 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	98.9 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=84; Group 3: N=87)	98.9 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3: N=87)	100.0 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=83; Group 3: N=87)	100.0 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16(Group 1: N=0; Group 2: N=0; Group 3: N=86)	NA percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20(Group 1: N=0; Group 2: N=0;Group 3: N=84)	NA percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24(Group 1: N=0; Group 2: N=0; Group 3: N=84)	NA percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20(Group 1: N=0; Group 2: N=0;Group 3: N=84)	NA percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=90; Group 2: N=87; Group 3: N=90)	14.9 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3: N=87)	98.8 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=84; Group 3: N=87)	98.8 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2 (Group 1: N=90; Group 2: N=87;Group 3: N=89)	49.4 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24(Group 1: N=0; Group 2: N=0; Group 3: N=84)	NA percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16(Group 1: N=0; Group 2: N=0; Group 3: N=86)	NA percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4 (Group 1: N=90; Group 2: N=87; Group 3: N=89)	80.5 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=83; Group 3: N=87)	98.8 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	97.6 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 16(Group 1: N=0; Group 2: N=0; Group 3: N=86)	97.7 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88)	98.9 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 8(Group 1: N=89; Group 2: N=84; Group 3: N=87)	100.0 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 10(Group 1: N=89; Group 2: N=84; Group 3: N=87)	100.0 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 20(Group 1: N=0; Group 2: N=0;Group 3: N=84)	100.0 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 12(Group 1: N=89; Group 2: N=83; Group 3: N=87)	97.7 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 1(Group 1: N=90; Group 2: N=87; Group 3: N=90)	11.1 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 24(Group 1: N=0; Group 2: N=0; Group 3: N=84)	100.0 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 2 (Group 1: N=90; Group 2: N=87;Group 3: N=89)	39.3 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24	Wk 4 (Group 1: N=90; Group 2: N=87; Group 3: N=89)	91.0 percentage of participants

Secondary

Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.

Time frame: Posttreatment Weeks 4 and 24

Population: Full Analysis Set

Arm	Measure	Group	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4	92.2 percentage of participants
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR24	83.3 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4	95.4 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR24	94.3 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4	90.0 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR24	87.8 percentage of participants

Secondary

Percentage of Participants With Virologic Failure

Virologic failure was defined as * On-treatment virologic failure * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ, while on treatment, * \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, * HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) * Relapse * HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement

Time frame: Up to Posttreatment Week 24

Population: Full Analysis Set

Arm	Measure	Value (NUMBER)
SOF/VEL 12 Weeks (Group 1)	Percentage of Participants With Virologic Failure	12.2 percentage of participants
SOF/VEL+RBV 12 Weeks (Group 2)	Percentage of Participants With Virologic Failure	3.4 percentage of participants
SOF/VEL 24 Weeks (Group 3)	Percentage of Participants With Virologic Failure	8.9 percentage of participants

Source: ClinicalTrials.gov · Data processed: Mar 12, 2026

Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score

Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24

Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

Percentage of Participants With Virologic Failure