A Study to Evaluate the Safety and Efficacy of the Combined Single Dose of Dactavira Plus Or Dactavira in Egyptian Adults With Chronic Genotype 4 HCV Infection

Hepatitis C Clinical Trial

Official title: A Phase 3 Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of the Combined Single Dose of Dactavira Plus (EPGCG, Sofosbuvir , Daclatasvir & Ribavirin) Versus Sofosbuvir + Daclatasvir + Ribavirin (Part A) and a Single Dose of Dactavira (EPGCG, Sofosbuvir & Daclatasvir) Versus Sofosbuvir + Daclatasvir (Part B) in Egyptian Adults With Chronic Genotype 4 HCV Infection

Status Completed

Clinical Trial Summary

A phase 3 Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of the combined single dose of Dactavira Plus (EPGCG, Sofosbuvir , Daclatasvir & Ribavirin) versus Sofosbuvir + Daclatasvir + Ribavirin (Part A) and a single dose of Dactavira (EPGCG, Sofosbuvir & Daclatasvir) versus Sofosbuvir + Daclatasvir (Part B) in Egyptian Adults with Chronic Genotype 4 HCV Infection.

Clinical Trial Description

Study Design: Part A Randomized, open-label study in treatment naïve cirrhotic adults with chronic genotype 4 HCV infection.

Treatment-naïve is defined as having never received treatment for HCV with any interferon (IFN), Ribavirin, or other approved or experimental HCV specific direct acting antivirals.

It is planned that 28 subjects will be enrolled in the study such that an approximate even number of treatment naïve subjects will be enrolled across the 2 treatment arms:

Arm 1 Single daily dose (2 Tablets) of Dactavira Plus each tablet contains (EPGCG 200 mg , Sofosbuvir 200mg, Daclatasvir 30 mg, Ribavirin 400 mg) for 12 weeks.

Arm 2 Daily dose including Sofosbuvir 400 mg , Daclatasvir 60 mg & Ribavirin 800 mg for 12 weeks.

Treatment assignments will be stratified according to the presence or absence of cirrhosis.

Diagnosis and Main Eligibility Criteria: HCV RNA > 104 IU/mL or HCV RNA > LLOQ and did not achieve SVR 12 after completing prior treatment in this study with chronic genotype 4 HCV infection. Treatment-naïve adults, male and non pregnant/non-lactating female subjects, ages 18 years or older.

Study Procedures/

Frequency: Study visits for all subjects will occur at screening, Baseline/Day 1. On-treatment visits will occur as follows:

• Part A, Arm 1 and 2 - at the end of Weeks 1, 2, 4, 8, 12.

• All subjects will complete a 4-Week Post-treatment visit regardless of treatment duration. Subjects with HCV RNA < LLOQ will continue to 12 Week Post treatment visits unless confirmed viral relapse occurs at which time subjects will be early terminated from the study.

Screening assessments include safety laboratory tests (chemistry, hematology, coagulation, and urinalysis), 12 lead ECG, HCV RNA, hemoglobin A1c, urine drug screen, liver imaging, serum B-hCG (for all female subjects of child-bearing potential), physical examination (with height and bodyweight), vital signs, medical history, concomitant medications, and adverse events.

On-treatment assessments include safety laboratory tests (chemistry, hematology, and coagulation), HCV RNA, urine pregnancy tests (for all female subjects of child-bearing potential), physical examination, vital signs, concomitant medications, and adverse events.

Post-treatment assessments include HCV RNA, urine pregnancy tests (for all female subjects of child-bearing potential), vital signs, concomitant medications, and adverse events.

Criteria for Evaluation:

Safety: Adverse events will be collected from baseline through the 4 Week Post-Treatment Visit and AEs related to study procedures, will be collected from when subjects sign the consent form. Clinical laboratory tests will be performed during treatment through the 12 Week Post-Treatment Visit.

Efficacy: Efficacy will be evaluated using scheduled assessments of HCV RNA performed using Gene Xpert HCV Test.

Statistical Methods: The primary efficacy endpoint is SVR12 (ie, HCV RNA < LLOQ 12 weeks post-treatment) in all subjects who are randomized and treated. No statistical hypothesis testing will be performed. For each of the two treatment groups, a 2-sided 95% confidence interval using the exact binomial distribution will be constructed.

All continuous endpoints will be summarized using an 8 number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) by treatment duration. All categorical endpoints will be summarized by number and percentage of subjects who meet the endpoint definition.

Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or using an 8 number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.

This study will be conducted in accordance with the guidelines of Good Clinical Practices (GCPs) including archiving of essential documents.

Study Design: Part B

Randomized, open-label study in treatment naïve not cirrhotic adults with chronic genotype 4 HCV infection.

Treatment-naïve is defined as having never received treatment for HCV with any interferon (IFN), Ribavirin, or other approved or experimental HCV specific direct acting antivirals.

It is planned that 50 subjects will be enrolled in the study such that an approximate even number of treatment naïve subjects will be enrolled across the 2 treatment arms:

Arm 3 Single daily dose (1 Tablets) of Dactavira each tablet contains (EPGCG 400 mg , Sofosbuvir 400mg, Daclatasvir 60 mg) for 12 weeks.

Arm 4 Daily dose including Sofosbuvir 400 mg & Daclatasvir 60 mg for 12 weeks

Treatment assignments will be stratified according to the presence or absence of cirrhosis.

Diagnosis and Main Eligibility Criteria: HCV RNA > 104 IU/mL or HCV RNA > LLOQ and did not achieve SVR 12 after completing prior treatment in this study with chronic genotype 4 HCV infection. Treatment-naïve adults, male and non pregnant/non-lactating female subjects, ages 18 years or older.

Study Procedures/

Frequency: Study visits for all subjects will occur at screening, Baseline/Day 1. On-treatment visits will occur as follows:

At the end of Weeks 1, 2, 4, 8, 12.

All subjects will complete a 4-Week Post-treatment visit regardless of treatment duration. Subjects with HCV RNA < LLOQ will continue to 12 Week Post treatment visits unless confirmed viral relapse occurs at which time subjects will be early terminated from the study.

Screening assessments include safety laboratory tests (chemistry, hematology, coagulation, and urinalysis), 12 lead ECG, HCV RNA, hemoglobin A1c, urine drug screen, liver imaging, serum B-hCG (for all female subjects of child-bearing potential), physical examination (with height and bodyweight), vital signs, medical history, concomitant medications, and adverse events.

On-treatment assessments include safety laboratory tests (chemistry, hematology, and coagulation), HCV RNA, urine pregnancy tests (for all female subjects of child-bearing potential), physical examination, vital signs, concomitant medications, and adverse events.

Post-treatment assessments include HCV RNA, urine pregnancy tests (for all female subjects of child-bearing potential), vital signs, concomitant medications, and adverse events.

Criteria for Evaluation:

Safety: Adverse events will be collected from baseline through the 4 Week Post-Treatment Visit and AEs related to study procedures, will be collected from when subjects sign the consent form. Clinical laboratory tests will be performed during treatment through the 12 Week Post-Treatment Visit.

Efficacy: Efficacy will be evaluated using scheduled assessments of HCV RNA performed using Gene Xpert HCV Test.

Statistical Methods:

The primary efficacy endpoint is SVR12 (ie, HCV RNA < LLOQ 12 weeks post-treatment) in all subjects who are randomized and treated. No statistical hypothesis testing will be performed. For each of the two treatment groups, a 2-sided 95% confidence interval using the exact binomial distribution will be constructed.

All continuous endpoints will be summarized using an 8 number summary (n, mean, standard deviation, and median, Q1, Q3, minimum, maximum) by treatment duration. All categorical endpoints will be summarized by number and percentage of subjects who meet the endpoint definition.

Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or using an 8 number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group. ;

Related Conditions & MeSH terms

• Hepatitis C

• NCT number: NCT03186313
• Study type: Interventional
• Source: Egyptian Liver Hospital
• Status: Completed
• Phase: Phase 3
• Start date: September 2016
• Completion date: November 30, 2017