Hepatitis C Virus Infection
Conditions
Keywords
Communicable Diseases, Hepatitis, Hepatitis C, Virus Diseases, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Velpatasvir, RNA Virus Infections, Ribavirin, Sofosbuvir, Antiviral Agents, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Anti-Infective Agents, Decompensated Cirrhosis
Brief summary
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) with or without ribavirin (RBV) for 12 weeks in adults with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis.
Interventions
DRUGSOF/VEL
400/100 mg FDC tablet administered orally once daily
DRUGRBV
Capsules administered orally in a divided daily dose
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Chronic HCV-infected males and non-pregnant/non-lactating females * Treatment naive or treatment experienced individuals * Child-Pugh-Turcotte Score 7-12 at screening Note: Other protocol defined Inclusion/
Exclusion criteria
may apply.
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; ie, 15 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Up to 12 weeks | — |
| Change From Baseline in HCV RNA | Baseline and up to 12 weeks | — |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment. |
| Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | Baseline to Posttreatment Week 24 | 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. |
| Percentage of Participants With Virologic Failure | Up to Posttreatment Week 24 | 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). |
| Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | Baseline to Posttreatment Week 24 | 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. |
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment. |
Countries
Japan
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| SOF/VEL SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | 51 |
| SOF/VEL + RBV 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 | 51 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 3 |
Baseline characteristics
| Characteristic | Total | SOF/VEL + RBV | SOF/VEL |
|---|---|---|---|
| Age, Continuous | 66 Years STANDARD_DEVIATION 9.5 | 66 Years STANDARD_DEVIATION 9.6 | 66 Years STANDARD_DEVIATION 9.6 |
| Child-Pugh-Turcotte (CPT) Class CPT A [5-6] | 3 Participants | 2 Participants | 1 Participants |
| Child-Pugh-Turcotte (CPT) Class CPT B [7-9] | 79 Participants | 39 Participants | 40 Participants |
| Child-Pugh-Turcotte (CPT) Class CPT C [10-15] | 20 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 51 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV genotype Genotype 1 | 80 Participants | 39 Participants | 41 Participants |
| HCV genotype Genotype 2 | 20 Participants | 11 Participants | 9 Participants |
| HCV genotype Genotype 3 | 1 Participants | 0 Participants | 1 Participants |
| HCV genotype Missing | 1 Participants | 1 Participants | 0 Participants |
| HCV RNA Category < 800,000 IU/mL | 60 Participants | 30 Participants | 30 Participants |
| HCV RNA Category ≥ 800,000 IU/mL | 42 Participants | 21 Participants | 21 Participants |
| HCV RNA (log10 international units per milliliter [IU/mL]) | 5.8 log10 IU/mL STANDARD_DEVIATION 0.63 | 5.8 log10 IU/mL STANDARD_DEVIATION 0.55 | 5.7 log10 IU/mL STANDARD_DEVIATION 0.7 |
| IL28b Status CC | 70 Participants | 37 Participants | 33 Participants |
| IL28b Status CT | 29 Participants | 13 Participants | 16 Participants |
| IL28b Status TT | 3 Participants | 1 Participants | 2 Participants |
| Model for End Stage Liver Disease (MELD) Score Category 10-15 MELD Score | 69 Participants | 33 Participants | 36 Participants |
| Model for End Stage Liver Disease (MELD) Score Category < 10 MELD Score | 25 Participants | 15 Participants | 10 Participants |
| Model for End Stage Liver Disease (MELD) Score Category 16-20 MELD Score | 6 Participants | 2 Participants | 4 Participants |
| Model for End Stage Liver Disease (MELD) Score Category 21-25 MELD Score | 1 Participants | 1 Participants | 0 Participants |
| Model for End Stage Liver Disease (MELD) Score Category > 25 MELD Score | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 102 Participants | 51 Participants | 51 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 62 Participants | 29 Participants | 33 Participants |
| Sex: Female, Male Male | 40 Participants | 22 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 3 / 51 |
| other Total, other adverse events | 14 / 51 | 34 / 51 |
| serious Total, serious adverse events | 4 / 51 | 7 / 51 |
Outcome results
Primary
Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Discontinuation of SOF/VEL | 0 Percentage of participants |
| SOF/VEL | Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Discontinuation of RBV | NA Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Discontinuation of SOF/VEL | 3.9 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Discontinuation of RBV | 17.6 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; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Time frame: Posttreatment Week 12
Population: Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 92.2 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | 92.2 Percentage of participants |
Comparison: 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.p-value: <0.0012-sided exact 1-sample binomial test
Comparison: 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.p-value: <0.0012-sided exact 1-sample binomial test
Secondary
Change From Baseline in HCV RNA
Time frame: Baseline and up to 12 weeks
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 2 | -4.14 log10 IU/mL | Standard Deviation 0.573 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 4 | -4.55 log10 IU/mL | Standard Deviation 0.696 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 8 | -4.56 log10 IU/mL | Standard Deviation 0.705 |
| SOF/VEL | Change From Baseline in HCV RNA | Change at Week 12 | -4.56 log10 IU/mL | Standard Deviation 0.705 |
| SOF/VEL + RBV | Change From Baseline in HCV RNA | Change at Week 12 | -4.70 log10 IU/mL | Standard Deviation 0.554 |
| SOF/VEL + RBV | Change From Baseline in HCV RNA | Change at Week 2 | -4.33 log10 IU/mL | Standard Deviation 0.525 |
| SOF/VEL + RBV | Change From Baseline in HCV RNA | Change at Week 8 | -4.70 log10 IU/mL | Standard Deviation 0.554 |
| SOF/VEL + RBV | Change From Baseline in HCV RNA | Change at Week 4 | -4.65 log10 IU/mL | Standard Deviation 0.528 |
Secondary
Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment
Time frame: Up to 12 weeks
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 2 | 45.1 Percentage of participants |
| SOF/VEL | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 4 | 96.1 Percentage of participants |
| SOF/VEL | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 8 | 100.0 Percentage of participants |
| SOF/VEL | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 12 | 100.0 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 12 | 100.0 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 2 | 51.0 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 8 | 96.1 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Week 4 | 90.2 Percentage of participants |
Secondary
Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score
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
Population: Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | Decrease (Improvement) | 38.3 Percentage of participants |
| SOF/VEL | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | No Change | 53.2 Percentage of participants |
| SOF/VEL | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | Increase (Worsening) | 8.5 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | Decrease (Improvement) | 21.7 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | No Change | 54.3 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score | Increase (Worsening) | 23.9 Percentage of participants |
Secondary
Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class
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
Population: Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF/VEL | Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | Worsened CPT Class | 4.3 Percentage of participants |
| SOF/VEL | Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | Improved CPT Class | 36.2 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | Improved CPT Class | 39.1 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With Improved and Worsened Child-Pugh-Turcotte (CPT) Class | Worsened CPT Class | 2.2 Percentage of participants |
Secondary
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Time frame: Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 92.2 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) | 92.2 Percentage of participants |
Secondary
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 94.1 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | 96.1 Percentage of participants |
Secondary
Percentage of Participants With Virologic Failure
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
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF/VEL | Percentage of Participants With Virologic Failure | 7.8 Percentage of participants |
| SOF/VEL + RBV | Percentage of Participants With Virologic Failure | 3.9 Percentage of participants |