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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SOF/VEL | Experimental | SOF/VEL for 12 weeks |
|
| SOF/VEL + RBV | Experimental | SOF/VEL + RBV for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SOF/VEL | Drug | 400/100 mg FDC tablet administered orally once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Posttreatment Week 12 |
| Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Up to 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Posttreatment Week 4 |
| Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) |
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Key Inclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Gilead Study Director | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shimonoseki | Yamaguchi | Japan | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | 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. |
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Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/about/ethics-and-code-of-conduct/policies.
18 months after study completion
A secured external environment with username, password, and RSA code.
155 participants were screened.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | SOF/VEL | Sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks |
| FG001 | SOF/VEL + RBV | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 17, 2016 | Dec 21, 2018 |
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| RBV | Drug | Capsules administered orally in a divided daily dose |
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SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment. |
| Posttreatment Week 24 |
| 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 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. | Baseline to Posttreatment Week 24 |
| 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. | Baseline to Posttreatment Week 24 |
| 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). | Up to Posttreatment Week 24 |
| Bunkyō City |
| Japan |
| Chiba | Japan |
| Chūō | Japan |
| Ehime | Japan |
| Fukui | Japan |
| Fukuyama-shi | Japan |
| Hiroshima | Japan |
| Ibaraki | Japan |
| Ichikawa | Japan |
| Iizuka | Japan |
| Iruma | Japan |
| Izunokuni | Japan |
| Kashibara | Japan |
| Kofu | Japan |
| Kumamoto | Japan |
| Kurume | Japan |
| Kyoto | Japan |
| Miyazaki | Japan |
| Morioka | Japan |
| Musashino | Japan |
| Nagoya | Japan |
| Nishinomiya | Japan |
| Okayama | Japan |
| Osaka | Japan |
| Ōmura | Japan |
| Sapporo | Japan |
| Sendai | Japan |
| Shimotsuga-gun | Japan |
| Suita | Japan |
| Takamatsu | Japan |
| Ube | Japan |
| Yamagata | Japan |
| COMPLETED |
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| NOT COMPLETED |
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Safety Analysis Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | SOF/VEL | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks |
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| HCV genotype | Count of Participants | Participants |
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| IL28b Status | The CC, CT, and TT alleles are different forms of the IL28b gene. | Count of Participants | Participants |
| |||||||||||||||
| HCV RNA (log10 international units per milliliter [IU/mL]) | Mean | Standard Deviation | log10 IU/mL |
| |||||||||||||||
| HCV RNA Category | Count of Participants | Participants |
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| Model for End Stage Liver Disease (MELD) Score Category | MELD score is a chronic liver disease severity scoring system. Scores can range from 6 to 40, with higher scores indicating greater disease severity. | Count of Participants | Participants |
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| 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. During screening/randomization, CPT scores may have been assessed using either the international normalized ratio (INR) or prothrombin activation percentage for the coagulation parameter. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | Posttreatment Week 12 |
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| Primary | Percentage of Participants Who Discontinued Treatment (SOF/VEL or RBV) Early Due to an Adverse Event | Safety Analysis Set | Posted | Number | Percentage of participants | Up to 12 weeks |
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| 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. | Full Analysis Set | Posted | Number | 95% Confidence Interval | Percentage of participants | Posttreatment Week 4 |
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| 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. | Full Analysis Set | Posted | Number | 95% Confidence Interval | Percentage of participants | Posttreatment Week 24 |
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| Secondary | Percentage of Participants Who Had HCV RNA < LLOQ by Visit While on Treatment | Participants in the Full Analysis Set with available data were analyzed. | Posted | Number | Percentage of participants | Up to 12 weeks |
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| Secondary | Change From Baseline in HCV RNA | Participants in the Full Analysis Set with available data were analyzed. | Posted | Mean | Standard Deviation | log10 IU/mL | Baseline and up to 12 weeks |
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| 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. | Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed. | Posted | Number | Percentage of participants | Baseline to Posttreatment Week 24 |
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| 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. | Participants in the Full Analysis Set who achieved SVR24 with available data were analyzed. | Posted | Number | Percentage of participants | Baseline to Posttreatment Week 24 |
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| 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). | Full Analysis Set | Posted | Number | Percentage of participants | Up to Posttreatment Week 24 |
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Adverse Events: Up to 12 weeks plus 30 days; All-Cause Mortality: Up to Posttreatment Week 24
Safety Analysis Set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SOF/VEL | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | 0 | 51 | 4 | 51 | 14 | 51 |
| EG001 | 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 | 3 | 51 | 7 | 51 | 34 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Gastric varices haemorrhage | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Varices oesophageal | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Bacterial sepsis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
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| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.1) | Systematic Assessment |
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| Rectal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (20.1) | Systematic Assessment |
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| Hepatic encephalopathy | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (20.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
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| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (20.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (20.1) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
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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:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gilead Clinical Study Information Center | Gilead Sciences | 1-833-445-3230 (GILEAD-0) | GileadClinicalTrials@gilead.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 27, 2018 | Dec 21, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D003141 | Communicable Diseases |
| D006505 | Hepatitis |
| D014777 | Virus Diseases |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006525 | Hepatitis, Viral, Human |
| D012327 | RNA Virus Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D007239 | Infections |
| D018178 | Flaviviridae Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000611331 | sofosbuvir-velpatasvir drug combination |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Genotype 2 |
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| Genotype 3 |
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| Missing |
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| CT |
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| TT |
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| ≥ 800,000 IU/mL |
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| 10-15 MELD Score |
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| 16-20 MELD Score |
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| 21-25 MELD Score |
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| > 25 MELD Score |
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| CPT B [7-9] |
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| CPT C [10-15] |
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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. |
| 2-sided exact 1-sample binomial test |
| <0.001 |
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%. |
| Superiority |
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| Participants |
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