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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Daclatasvir 60 MG Oral Tablet [Daklinza]; Drug: Sofosbuvir 400 MG Oral Tablet [Sovaldi]; Drug: Ribavirin Oral Product

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Ahmed Negida; Phone Number: +201125549087; Email: ahmed01251@medicine.zu.edu.eg
• Study Contact Backup: Name: Hussien Ahmed, MD; Phone Number: +201006037334; Email: hoseen011232@medicine.zu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will include male or female patients ≥ 18 years, HCV RNA≥ 104 IU/mL, HCV genotype 4, screening ECG without clinically significant abnormalities.

Description

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%).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zagazig University
• Collaborators: Cairo University
• Investigators: Study Director: Samah A Loutfy, National Cancer Institute, Cairo University, Cairo, Egypt

Publications and helpful links

General Publications

• 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.
• Jensen D, Sherman KE, Hezode 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.
• Hezode C, Alric L, Brown A, Hassanein T, Rizzetto M, Buti M, Bourliere 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. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2017
• Primary Completion (ANTICIPATED): December 31, 2018
• Study Completion (ANTICIPATED): December 31, 2018

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (ESTIMATE): May 13, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 10, 2017
• Last Update Submitted That Met QC Criteria: October 8, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Antiviral; Virologic Response; Hepatitis C virus genotype 4
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Sofosbuvir; Ribavirin
• Other Study ID Numbers: 2667-20-3-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED