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The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir (300 mg twice daily) given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) in Japanese participants with chronic hepatitis C (CHC) genotype (GT) 1 who have not responded to previous treatment. The primary efficacy objective is to estimate efficacy of vaniprevir, peg-IFN and RBV for 24 weeks as assessed by the percentage of participants achieving undetectable Hepatitis C Virus ribonucleic acid (HCV RNA) 24 weeks after completion of all study therapy (Sustained Viral Response 24 [SVR24]).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vaniprevir 24 Week Arm | Experimental | Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vaniprevir | Drug | Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 24 weeks |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response (SVR)24 | SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 24 weeks after 24 weeks of study therapy (up to 48 weeks) |
| Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) |
| Percentage of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving SVR12 | SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 12 weeks after 24 weeks of study therapy (up to 36 weeks) |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26936417 | Result | Kumada H, Mochida S, Suzuki F, Chayama K, Karino Y, Nakamura K, Fujimoto G, Howe AY, Ludmerer SW, Mobashery N. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies. J Gastroenterol Hepatol. 2016 Oct;31(10):1674-1683. doi: 10.1111/jgh.13328. | |
| 26947564 |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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42 participants were randomized to receive 24 weeks of vaniprevir in combination with 24 weeks of peg-IFN α-2b (peg-IFN) and ribavirin (RBV).
Japanese patients 20-70 years old (inclusive) with chronic, compensated, genotype 1 Hepatitis C (HCV) infection and HCV ribonucleic acid (RNA) levels ≥5.0 log IU/mL peripheral blood at screening, who had failed to respond to prior interferon treatment, were recruited from 10 sites in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vaniprevir 24 Week Arm | Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| peg-IFN | Biological | Open-label peg-IFN alfa-2b at 1.5 μg/kg once per week, administered subcutaneously (SC) for 24 weeks |
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| ribavirin | Drug | Capsules containing 200 mg RBV, orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 weeks |
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| Percentage of Participants Achieving Rapid Virologic Response (RVR) | RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | At Week 4 |
| Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | cEVR was defined as having an undetectable HCV RNA level at Week 12. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | At Week 12 |
| Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT) | Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | At Week 24 |
| Mean Change From Baseline in HCV RNA (Log 10) | HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable". | Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 |
| Ludmerer SW, Hirano T, Black S, Howe AY, Chang W, Takase A, Nakamura K, Tanaka Y, Kumada H, Hayashi N, Nickle D. HCV evolutionary genetics of SVR versus virologic failure assessed from the vaniprevir phase III registration trials. Antiviral Res. 2016 Jun;130:118-29. doi: 10.1016/j.antiviral.2016.03.004. Epub 2016 Mar 3. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Vaniprevir 24 Week Arm | Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment |
| Units | Counts |
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| 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 |
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| Sex: Female, Male | 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 Achieving Sustained Virologic Response (SVR)24 | SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | Full Analysis Set (FAS) population; all randomized participants who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | 24 weeks after 24 weeks of study therapy (up to 48 weeks) |
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| Primary | Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment | Posted | Number | 95% Confidence Interval | percentage of participants | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) |
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| Secondary | Percentage of Participants Achieving SVR12 | SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | FAS population; all randomized participants who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 weeks after 24 weeks of study therapy (up to 36 weeks) |
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| Secondary | Percentage of Participants Achieving Rapid Virologic Response (RVR) | RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | FAS population; all randomized participants who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 4 |
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| Secondary | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | cEVR was defined as having an undetectable HCV RNA level at Week 12. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | FAS population; all randomized participants who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 12 |
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| Secondary | Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT) | Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | FAS population; all randomized participants who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 24 |
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| Secondary | Mean Change From Baseline in HCV RNA (Log 10) | HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable". | FAS population; all randomized participants who received at least one dose of study treatment. | Posted | Mean | Standard Deviation | Log IU/ml | Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 |
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| Primary | Percentage of Participants Who Discontinued Study Drug Due to an AE | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. | All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment | Posted | Number | percentage of participants | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) |
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From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
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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 | Vaniprevir 24 Week Arm | Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment | 3 | 42 | 42 | 42 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia bacterial | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
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| Loss of consciousness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Bilirubin conjugated increased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Blood uric acid increased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President, Late Stage Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C540393 | vaniprevir |
| C417083 | peginterferon alfa-2b |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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