Determining the Sustained Virologic Response of Declatasvir in Egyptian Patients With Hepatitis C Virus Genotype 4
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Group 1: Easy to treat group 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]
Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein
Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]
Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor
|
| Group 2: Difficult to treat group 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]
Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein
Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]
Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor
Drug: Ribavirin Oral Product
Ribavirin (twice-daily) dosed according to body weight (<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily)
|
| Group 3: Sofosbuvir resistant cases 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]
Daclatasvir (60 MG) is a potent, pan-genotypic inhibitor of the HCV NS5A protein
Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]
Sofosbuvir (400 MG) is a nucleotide analogue HCV NS5B polymerase inhibitor
Drug: Ribavirin Oral Product
Ribavirin (twice-daily) dosed according to body weight (<75 kg, 1000 mg daily; ≥75 kg, 1200 mg daily)
|
Outcome Measures
Primary Outcome Measures
- 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] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Neutropenia: Grade 3, 500-749/mm3; Grade 4, <500/mm3
- Incidence of Lymphopenia [Safety] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Lymphopenia: Grade 3, 350-499/mm3; Grade 4, <350/mm3
- Incidence of anaemia [Safety] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Anaemia: Grade 3, haemoglobin 7.0-8.9 g/dL; Grade 4, <7.0 g/dL
- Incidence of Thrombocytopenia [Safety] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Thrombocytopenia: Grade 3, 25 000-49 999/mm3; Grade 4, <25 000/mm3
- Incidence of (Increased total Bilirubin) [Safety] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Bilirubin elevations: Grade 3, 2.6-5×ULN; Grade 4, >5×ULN
- Incidence of elevated Alanine Aminotransferase [Safety] [Within the treatment period (12 or 24 weeks according to the treatment regimen)]
Alanine Aminotransferase elevations: Grade 3, 5.1-10×upper limit of normal (ULN); Grade 4, >10×ULN
- 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
- Health Related Quality of Life (HRQoL) [24 weeks]
HRQoL will be assessed using the Arabic version of SF-36 questionnaire (SF-36™ Health Survey)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with HCV genotype 4
-
Age ≥ 18 years
-
HCV RNA≥ 104 IU/mL
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Screening ECG without clinically significant abnormalities.
Exclusion Criteria:
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Total serum bilirubin > 3 mg/dl.
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Serum albumin < 2.8 g/dl.
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INR ≥ 1.7
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Platelet count < 50000/mm3.
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Hepatic cell carcinoma except four weeks after intervention aiming to cure with no evidence of activity by dynamic imaging (CT or MRI).
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Extra hepatic malignancy except after two years of disease free interval
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Pregnancy or inability to use contraception.
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Inadequately controlled diabetes mellitus (HbA1c > 9%).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Zagazig University
- Cairo University
Investigators
- Study Director: Samah A Loutfy, National Cancer Institute, Cairo University, Cairo, Egypt
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Hézode C, Alric L, Brown A, Hassanein T, Rizzetto M, Buti M, Bourlière M, Thabut D, Molina E, Rustgi V, Samuel D, McPhee F, Liu Z, Yin PD, Hughes E, Treitel M; COMMAND-4 study team. Randomized controlled trial of the NS5A inhibitor daclatasvir plus pegylated interferon and ribavirin for HCV genotype-4 (COMMAND-4). Antivir Ther. 2015 Aug 27;21(3):195-205. doi: 10.3851/IMP2985. [Epub ahead of print]
- Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, de Ledinghen V, Tran A, Elkhashab M, Younes ZH, Kugelmas M, Mauss S, Everson G, Luketic V, Vierling J, Serfaty L, Brunetto M, Heo J, Bernstein D, McPhee F, Hennicken D, Mendez P, Hughes E, Noviello S; HALLMARK-QUAD Study Team. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.
- Wyles DL, Ruane PJ, Sulkowski MS, Dieterich D, Luetkemeyer A, Morgan TR, Sherman KE, Dretler R, Fishbein D, Gathe JC Jr, Henn S, Hinestrosa F, Huynh C, McDonald C, Mills A, Overton ET, Ramgopal M, Rashbaum B, Ray G, Scarsella A, Yozviak J, McPhee F, Liu Z, Hughes E, Yin PD, Noviello S, Ackerman P; ALLY-2 Investigators. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):714-25. doi: 10.1056/NEJMoa1503153. Epub 2015 Jul 21.
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