Randomized Clinical Trial of Sofosbuvir in Combination With Daclatasvir or Simeprevir for 12 Weeks in Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus Genotype 1 (TNT)

Study Overview
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Brief Summary
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The purpose of the study is to study the combination of Sofosbuvir in Combination With Daclatasvir or Simeprevir for 12 Weeks in Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus (HCV) Genotype 1.

Detailed Description
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In this open-label, single-center, head-to-head non-inferiority trial, treatment-naive or pegylated interferon treatment-experienced patients with GT1 infection were randomized to receive once-daily SOF 400 mg plus DCV 60 mg or SIM 150 mg for 12 weeks.

Official Title
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Randomized Clinical Trial to Assess the Effectiveness of Sofosbuvir in Combination With Daclatasvir or Simeprevir for 12 Weeks in Non-cirrhotic Subjects Infected With Chronic Hepatitis C Virus (HCV) Genotype 1 (TNT-1 Study)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Daclatasvir + Sofosbuvir
* Drug: Simeprevir + Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genotype 1 HCV infection confirmed a positive test for anti-HCV antibody and detectable serum HCV RNA by PCR Never taken DAAs for HCV Patients must be able to understand and agree to/comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications No Liver Cirrhosis Liver fibrosis Metavir F3 APRI > 1,5 FIB4 > 3,25 Exclusion Criteria: Infection with HCV other than GT-1 or subjects with mixed infections of any genotype Liver Cirrhosis Evidence of decompensated liver Subjects Infected with HIV-1 Hepatitis B virus (HBV) coinfection Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair Current or known history of cancer Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy Pregnancy or impossibility to use birth control methods by the couple, or breastfeeding Regular use of: erythromycin, clarithromycin, rifampicin, rifabutin, telithromycin, itraconazole, ketoconazole, posaconazole, fluconazole, voriconazole, dexamethasone, cisapride, rifapentine, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, St. John's wort (Hypericum perforatum), silymarin (Silybum marianum) and some antiarrhythmic drugs such as amiodarone

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclatasvir + Sofosbuvir<br>Daclatasvir 60 mg tablet + Sofosbuvir 400 mg tablet oral dosing once daily for 12 weeks | Drug: Daclatasvir + Sofosbuvir<br>* Sofosbuvir 400 mg tablet + Daclatasvir 60 mg tablet oral dosing once daily for 12 weeks<br>* Other names: Solvaldi, Daklinza;|
| Experimental: Simeprevir + Sofosbuvir<br>Simeprevir 150 mg tablet + Sofosbuvir 400 mg tablet oral dosing once daily for 12 weeks | Drug: Simeprevir + Sofosbuvir<br>* Sofosbuvir 400 mg tablet + Simeprevir 150 mg tablet oral dosing once daily for 12 weeks<br>* Other names: Sovaldi, Olysio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Non-cirrhotic Subjects With Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 12 IU/mL at follow-up Week 12 | At follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Rapid Virologic Response at Week 4 (RVR) | RVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 12 IU/mL at Week 4. | Week 4 | 
| Percentage of Subjects With End of Treatment Response (EOTR) | EOTR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 12 IU/mL at the end of treatment. | Week 12 | 
| Treatment safety measured by the number of incidence of serious adverse event (SAEs), discontinuations due to adverse event (AEs), Grade 3/4 AEs and Grade 3/4 clinical laboratory abnormalities through the end of treatment. |  | From start of study treatment up to 7 days post last dose of study treatment | 
| Percentage of Genotype 1 Hepatitis C Virus (HCV)-Infected Non-cirrhotic Subjects With Relapse at Follow-up Week 12 (SVR12) | Relapse was defined as hepatitis C virus RNA levels to be > lower limit of quantitation ie, 12 IU/mL at follow-up Week 12 | At follow-up Week 12 |