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Efficacy and Safety of Sofosbuvir/Velpatasvir ± Ribavirin for 12 Weeks in Adults With Chronic HCV Infection and Decompensated Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02996682
Recruitment Status : Completed
First Posted : December 19, 2016
Results First Posted : February 26, 2019
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Interventions Drug: SOF/VEL
Drug: RBV
Enrollment 102
Recruitment Details Participants were enrolled at study sites in Japan. The first participant was screened on 26 December 2016. The last study visit occurred on 08 May 2018.
Pre-assignment Details 155 participants were screened.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description Sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks SOF/VEL (400/100 mg) FDC tablet once daily + ribavirin (RBV) capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Period Title: Overall Study
Started 51 51
Completed 51 48
Not Completed 0 3
Reason Not Completed
Death             0             3
Arm/Group Title SOF/VEL SOF/VEL + RBV Total
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 51 51 102
Hide Baseline Analysis Population Description
Safety Analysis Set included all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 51 participants 102 participants
66  (9.6) 66  (9.6) 66  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Female
33
  64.7%
29
  56.9%
62
  60.8%
Male
18
  35.3%
22
  43.1%
40
  39.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
51
 100.0%
51
 100.0%
102
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
51
 100.0%
51
 100.0%
102
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
HCV genotype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
Genotype 1
41
  80.4%
39
  76.5%
80
  78.4%
Genotype 2
9
  17.6%
11
  21.6%
20
  19.6%
Genotype 3
1
   2.0%
0
   0.0%
1
   1.0%
Missing
0
   0.0%
1
   2.0%
1
   1.0%
IL28b Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
CC
33
  64.7%
37
  72.5%
70
  68.6%
CT
16
  31.4%
13
  25.5%
29
  28.4%
TT
2
   3.9%
1
   2.0%
3
   2.9%
[1]
Measure Description: The CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA (log10 international units per milliliter [IU/mL])  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 51 participants 51 participants 102 participants
5.7  (0.70) 5.8  (0.55) 5.8  (0.63)
HCV RNA Category  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
< 800,000 IU/mL
30
  58.8%
30
  58.8%
60
  58.8%
≥ 800,000 IU/mL
21
  41.2%
21
  41.2%
42
  41.2%
Model for End Stage Liver Disease (MELD) Score Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
< 10 MELD Score
10
  19.6%
15
  29.4%
25
  24.5%
10-15 MELD Score
36
  70.6%
33
  64.7%
69
  67.6%
16-20 MELD Score
4
   7.8%
2
   3.9%
6
   5.9%
21-25 MELD Score
0
   0.0%
1
   2.0%
1
   1.0%
> 25 MELD Score
1
   2.0%
0
   0.0%
1
   1.0%
[1]
Measure Description: MELD score is a chronic liver disease severity scoring system. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Child-Pugh-Turcotte (CPT) Class   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 51 participants 102 participants
CPT A [5-6]
1
   2.0%
2
   3.9%
3
   2.9%
CPT B [7-9]
40
  78.4%
39
  76.5%
79
  77.5%
CPT C [10-15]
10
  19.6%
10
  19.6%
20
  19.6%
[1]
Measure Description: CPT is a chronic liver disease classification system. Classes include CPT Class A, CPT Class B, and CPT Class C, in order of greater disease severity. During screening/randomization, CPT scores may have been assessed using either the international normalized ratio (INR) or prothrombin activation percentage for the coagulation parameter.
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Hide Description SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time Frame Posttreatment Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92.2
(81.1 to 97.8)
92.2
(81.1 to 97.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF/VEL
Comments A sample size of 50 participants in each treatment group would provide over 99% power to detect at least 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 0.025.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value was from the 2-sided exact 1-sample binomial test for the superiority of each treatment group over pre-specified rate of 1%.
Method 2-sided exact 1-sample binomial test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SOF/VEL + RBV
Comments A sample size of 50 participants in each treatment group would provide over 99% power to detect at least 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 0.025.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-value was from the 2-sided exact 1-sample binomial test for the superiority of each treatment group over pre-specified rate of 1%.
Method 2-sided exact 1-sample binomial test
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Unit of Measure: Percentage of participants
Discontinuation of SOF/VEL 0 3.9
Discontinuation of RBV NA [1]  17.6
[1]
RBV drug was not used an as intervention in this arm.
3.Secondary Outcome
Title Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Hide Description SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
Time Frame Posttreatment Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
94.1
(83.8 to 98.8)
96.1
(86.5 to 99.5)
4.Secondary Outcome
Title Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
Hide Description SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
Time Frame Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
92.2
(81.1 to 97.8)
92.2
(81.1 to 97.8)
5.Secondary Outcome
Title Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 Number Analyzed 51 participants 51 participants
45.1 51.0
Week 4 Number Analyzed 51 participants 51 participants
96.1 90.2
Week 8 Number Analyzed 51 participants 51 participants
100.0 96.1
Week 12 Number Analyzed 51 participants 49 participants
100.0 100.0
6.Secondary Outcome
Title Change From Baseline in HCV RNA
Hide Description [Not Specified]
Time Frame Baseline and up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Week 2 Number Analyzed 51 participants 51 participants
-4.14  (0.573) -4.33  (0.525)
Change at Week 4 Number Analyzed 51 participants 51 participants
-4.55  (0.696) -4.65  (0.528)
Change at Week 8 Number Analyzed 51 participants 49 participants
-4.56  (0.705) -4.70  (0.554)
Change at Week 12 Number Analyzed 51 participants 49 participants
-4.56  (0.705) -4.70  (0.554)
7.Secondary Outcome
Title Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score
Hide Description MELD score is a chronic liver disease severity scoring system. Scores can range from 6 to 40, with higher scores indicating greater disease severity. "No change" was assigned for differences (posttreatment visits minus baseline score) of -1, 0 or 1; "Decrease" was assigned for differences that were less than or equal to -2; and "Increase" was assigned for values that were greater than or equal to 2.
Time Frame Baseline to Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 47 46
Measure Type: Number
Unit of Measure: Percentage of participants
Decrease (Improvement) 38.3 21.7
No Change 53.2 54.3
Increase (Worsening) 8.5 23.9
8.Secondary Outcome
Title Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class
Hide Description CPT is a chronic liver disease classification system. Classes include CPT Class A, CPT Class B, and CPT Class C, in order of greater disease severity. Participants with improved CPT class was defined as having Class C at Baseline and Class B or A at Posttreatment Week 24 or Class B at Baseline and Class A at Posttreatment Week 24. Participants with worsened CPT class was defined as having Class A at Baseline and Class B or C at Posttreatment Week 24 or Class B at Baseline and Class C at Posttreatment Week 24. CPT scores were calculated using prothrombin activation percentage for the coagulation parameter per Japan's standard.
Time Frame Baseline to Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed.
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 47 46
Measure Type: Number
Unit of Measure: Percentage of participants
Improved CPT Class 36.2 39.1
Worsened CPT Class 4.3 2.2
9.Secondary Outcome
Title Percentage of Participants With Virologic Failure
Hide Description

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), or Relapse (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).

Time Frame Up to Posttreatment Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks
SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
Overall Number of Participants Analyzed 51 51
Measure Type: Number
Unit of Measure: Percentage of participants
7.8 3.9
Time Frame Adverse Events: Up to 12 weeks plus 30 days; All-Cause Mortality: Up to Posttreatment Week 24
Adverse Event Reporting Description Safety Analysis Set included all participants who received at least 1 dose of study drug.
 
Arm/Group Title SOF/VEL SOF/VEL + RBV
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks SOF/VEL (400/100 mg) FDC tablet once daily + RBV capsules (600, 800, or 1,000 mg daily based on weight and CPT class) for 12 weeks
All-Cause Mortality
SOF/VEL SOF/VEL + RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)   3/51 (5.88%) 
Show Serious Adverse Events Hide Serious Adverse Events
SOF/VEL SOF/VEL + RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   4/51 (7.84%)   7/51 (13.73%) 
Blood and lymphatic system disorders     
Anaemia  1  0/51 (0.00%)  1/51 (1.96%) 
Gastrointestinal disorders     
Ascites  1  0/51 (0.00%)  1/51 (1.96%) 
Gastric varices haemorrhage  1  0/51 (0.00%)  1/51 (1.96%) 
Oesophageal varices haemorrhage  1  0/51 (0.00%)  1/51 (1.96%) 
Varices oesophageal  1  1/51 (1.96%)  0/51 (0.00%) 
Infections and infestations     
Bacterial sepsis  1  0/51 (0.00%)  1/51 (1.96%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/51 (0.00%)  2/51 (3.92%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Gastric cancer  1  1/51 (1.96%)  0/51 (0.00%) 
Rectal adenocarcinoma  1  1/51 (1.96%)  0/51 (0.00%) 
Nervous system disorders     
Hepatic encephalopathy  1  1/51 (1.96%)  2/51 (3.92%) 
Renal and urinary disorders     
Acute kidney injury  1  0/51 (0.00%)  1/51 (1.96%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF/VEL SOF/VEL + RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   14/51 (27.45%)   34/51 (66.67%) 
Blood and lymphatic system disorders     
Anaemia  1  0/51 (0.00%)  19/51 (37.25%) 
Haemolytic anaemia  1  0/51 (0.00%)  3/51 (5.88%) 
Thrombocytopenia  1  0/51 (0.00%)  3/51 (5.88%) 
Gastrointestinal disorders     
Diarrhoea  1  0/51 (0.00%)  7/51 (13.73%) 
General disorders     
Oedema peripheral  1  3/51 (5.88%)  2/51 (3.92%) 
Infections and infestations     
Nasopharyngitis  1  7/51 (13.73%)  3/51 (5.88%) 
Gastroenteritis  1  3/51 (5.88%)  0/51 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  1/51 (1.96%)  3/51 (5.88%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/51 (0.00%)  4/51 (7.84%) 
Nervous system disorders     
Headache  1  1/51 (1.96%)  4/51 (7.84%) 
Psychiatric disorders     
Insomnia  1  0/51 (0.00%)  4/51 (7.84%) 
Skin and subcutaneous tissue disorders     
Rash  1  4/51 (7.84%)  1/51 (1.96%) 
1
Term from vocabulary, MedDRA (20.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

  • The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or
  • The study has been completed at all study sites for at least 2 years
Results Point of Contact
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Publications of Results:
Takehara T, Kurosaki M, Tanaka Y, Tatsumi T, Ikeda F, Takikawa Y, et al. Sofosbuvir/Velpatasvir with or without Ribavirin for 12 Weeks in HCV-Infected Japanese Subjects with Decompensated Cirrhosis [Presentation]. 54th Annual Meeting of Japan Society of Hepatology; 2018 June 15; Osaka, Japan.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02996682     History of Changes
Other Study ID Numbers: GS-US-342-4019
First Submitted: December 15, 2016
First Posted: December 19, 2016
Results First Submitted: February 1, 2019
Results First Posted: February 26, 2019
Last Update Posted: February 26, 2019