Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Tablet Plus Ribavirin Tablet (Part A) Versus Single Dose (2 Tablets) of EHCV Containing Sofosbuvir, Ribavirin, and Natural Anti-hemolytic (B) in Egyptian Adults With Chronic Genotype 4 HCV Infection

Hepatitis c Clinical Trial

Official title: Randomized, Open-Label, Study to Evaluate the Safety and Efficacy of Sofosbuvir Tablet Plus Ribavirin Tablet (Part A) Versus Single Dose (2 Tablets) of EHCV Containing Sofosbuvir, Ribavirin, and Natural Anti-hemolytic (B) in Egyptian Adults With Chronic Genotype 4 HCV Infection

Status Completed

Clinical Trial Summary

Two Groups of Genotype 4 HCV Patients will participate through open-label randomized Study comparing Sofosbuvir tablet Plus Ribavirin tablet (Part A) versus single Dose (2 tablets) of EHCV containing Sofosbuvir, Ribavirin, and Natural anti-hemolytic (B) evaluating the safety and efficacy for both arms.

Sponsor: Wadi El Nil Hospital

Study Centers Planned: Approximately 2 sites in Egypt

Clinical Trial Description

Study Design:

Part A

Randomized, open-label study in treatment naïve and treatment experienced adults with chronic genotype 4 HCV infection.

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

Treatment-experienced is defined as:

1. IFN Intolerant

2. Non-response

3. Relapse/Breakthrough

It is planned that 40 + 40 subjects will be enrolled in the study such that an approximate even number of treatment naïve and treatment experienced subjects will be enrolled across the 2 treatment arms:

Arm 1 Sofosbuvir 400 mg once daily +RBV (1000 mg/day) for 12-24 weeks

Arm 2 Single Dose (2 tablets) once daily each tablet containing SOF 200 mg, RBV 500 mg, and Natural anti-hemolytic (AH) at 200 mg for 12-24 weeks Treatment assignments will be stratified according to prior treatment experience and the presence or absence of cirrhosis.

Cohorts:

Cohort is a single-arm, open-label, non-randomized design in subjects who completed treatment in Part A of the study with SOF+RBV for 12-24 weeks or in Part B of the study with single dose EHCV (2 Tablet) containing SOF/RBV/AH FDC for 12-24 weeks.

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 or treatment experienced adults, male and non-pregnant/non-lactating female subjects, ages 18 years or older. See Section 1 and 1.2 of the protocol for detailed Inclusion and Exclusion criteria.

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, 6, 8, 10, 12, 16, 20, and 24 All subjects will complete a 4-Week Post-treatment visit regardless of treatment duration. Subjects with HCV RNA < LLOQ will continue to 12 Week and 24 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, serology (HBV, and HIV), 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. In addition, subjects being screened for Part A and Part B (Cohort 1) will have HCV genotyping and IL28B genotyping performed.

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.

Samples will be collected at Baseline/Day 1 and every visit Plasma samples will be collected during treatment visits for pharmacokinetic (PK) analysis of study drug (Part A only). Untested samples will be archived for up to 10 years.

Test Product, Dose, and Mode of Administration: SOF is manufactured as a 400 mg tablet for oral administration. Subjects will take 1 tablet for a total dose of 400 mg orally once daily in the morning with RBV (1000 mg) splitted on 2 doses daily 600 mg on morning and 400 mg on evening and with food for 12-24 weeks.

The fixed dose EHCV combinations in Single Dose (2 tablets) once daily each tablet containing SOF 200 mg, RBV 500 mg, and Natural anti-hemolytic (AH) at 200 mg. Subjects will take 2 tablet with food for 12-24 weeks.

Reference Therapy, Dose, and Mode of Administration: None

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 COBAS® TaqMan® HCV Test, v2.0 for Use with the High Pure System.

PK Part A only. A single PK blood sample will be collected at all study visits while on Treatment.

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.

Part A: With a sample size of 40 subjects in each arm, a two sided 95% exact confidence interval will extend at most 29% in length.

Part B: With a sample size of 40 subjects in each treatment group in Cohort 1, a 2-sided 95% exact confidence interval will extend at most 32% in length.

Secondary efficacy endpoints include the proportion of subjects with SVR4 and SVR24.

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.

Data from Part B will be analyzed separately from Part A and may be reported separately.

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

Related Conditions & MeSH terms

• Hepatitis c

• NCT number: NCT02483156
• Study type: Interventional
• Source: Egyptian Liver Hospital
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2015