Determining the Sustained Virologic Response of Declatasvir in Egyptian Patients With Hepatitis C Virus Genotype 4

Study Overview
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Brief Summary
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This is a prospective, cohort study in Faculty of Medicine, Zagazig University, Egypt. From June to December, 2016, investigators will follow up patients with chronic Hepatitis C virus genotype 4 receiving daclatasvir-sofosbuvir treatment regimen within the national program of Egyptian ministry of health and population. The primary outcomes are safety of the treatment and the sustained virologic response 12 weeks after discontinuation of therapy. For the secondary outcomes, investigators will measure the change in health related quality of life and investigate the genetic sequence of viral RNA of resistant patients.

Official Title
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Determining the Sustained Virologic Response of Declatasvir in Egyptian Patients With Hepatitis C Virus Genotype 4

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]
* Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]
* Drug: Ribavirin Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with HCV genotype 4 Age ≥ 18 years HCV RNA≥ 104 IU/mL Screening ECG without clinically significant abnormalities. Exclusion Criteria: Total serum bilirubin > 3 mg/dl. Serum albumin < 2.8 g/dl. INR ≥ 1.7 Platelet count < 50000/mm3. Hepatic cell carcinoma except four weeks after intervention aiming to cure with no evidence of activity by dynamic imaging (CT or MRI). Extra hepatic malignancy except after two years of disease free interval Pregnancy or inability to use contraception. Inadequately controlled diabetes mellitus (HbA1c > 9%).

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1: Easy to treat group<br>Treatment naïve Total serum bilirubin ≤ 1.2 mg/dl Serum albumin ≥ 3.5 g/dl International normalized ratio ≤ 1.2 Platelet count ≥ 150000 mm3 This group will be receiving Sofosbuvir + daclatasvir for 12 weeks. | Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]<br>* Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein<br>Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]<br>* Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor<br>|
| Group 2: Difficult to treat group<br>Peg interferon treatment experienced. Total serum bilirubin ≥ 1.2 mg/dl Serum albumin ≤ 3.5 g/dl International normalized ratio ≥ 1.2 Platelet count ≤ 150000 mm3 This group will be receiving Sofosbuvir + daclatasvir + ribavirin for 12 weeks. | Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]<br>* Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein<br>Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]<br>* Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor<br>Drug: Ribavirin Oral Product<br>* Ribavirin (twice-daily) dosed according to body weight (<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily)<br>|
| Group 3: Sofosbuvir resistant cases<br>This is the group of patients who failed in previous Sofosbuvir treatment regiment. This group will be receiving Sofosbuvir + daclatasvir + ribavirin for 24 weeks. | Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]<br>* Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein<br>Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]<br>* Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor<br>Drug: Ribavirin Oral Product<br>* Ribavirin (twice-daily) dosed according to body weight (<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy measured by Sustained Virologic Response Rate |  | 12 weeks posttreatment | 
| Incidence of grade 3/4 adverse events [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Neutropenia [Safety] | Neutropenia: Grade 3, 500-749/mm3; Grade 4, <500/mm3 | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Lymphopenia [Safety] | Lymphopenia: Grade 3, 350-499/mm3; Grade 4, <350/mm3 | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of anaemia [Safety] | Anaemia: Grade 3, haemoglobin 7.0-8.9 g/dL; Grade 4, <7.0 g/dL | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Thrombocytopenia [Safety] | Thrombocytopenia: Grade 3, 25 000-49 999/mm3; Grade 4, <25 000/mm3 | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of (Increased total Bilirubin) [Safety] | Bilirubin elevations: Grade 3, 2.6-5×ULN; Grade 4, >5×ULN | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of elevated Alanine Aminotransferase [Safety] | Alanine Aminotransferase elevations: Grade 3, 5.1-10×upper limit of normal (ULN); Grade 4, >10×ULN | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Fatigue [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Headache [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Pruritus [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Insomnia [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Rash [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Nausea [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 
| Incidence of Myalgia [Safety] |  | Within the treatment period (12 or 24 weeks according to the treatment regimen) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life (HRQoL) | HRQoL will be assessed using the Arabic version of SF-36 questionnaire (SF-36™ Health Survey) | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C virus genotype 4, Antiviral, Virologic Response