Sofosbuvir Plus Daclatasvir With or Without Ribavirin and Chronic HCV Genotype (GT) 4

Sponsor

Beni-Suef University (Other)

Overall Status

Completed

CT.gov ID

NCT04387526

Collaborator

(none)

946

Enrollment

Arms

Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to evaluate the efficacy and safety of DCV plus sofosbuvir (SOF) with or without ribavirin (RBV) for treatment of Egyptian participants infected with HCV GT4.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus Infection	Drug: (SOF and DCV) Drug: (SOF, DCV, and RBV)	Phase 2/Phase 3

Detailed Description

Egyptian participants infected with HCV GT4 were classified into two groups: group 1 (easy to treat) was treated with a dual therapy of SOF/DCV daily for 12 weeks and group 2 (difficult to treat) was treated with a triple therapy of SOF/DCV/RBV daily for 12 weeks.

SOF dose was 400 mg/day given orally DCV was given in a dose of 60 mg/day, orally. RBV was given as oral tablets in the morning and in the evening based on patient's weight and tolerability (starting dose 600 mg/day to reach 1200 mg/day.

Study Design

Study Type:

Interventional

Actual Enrollment :

946 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Sofosbuvir Plus Daclatasvir With or Without Ribavirin: Large Real-life Results of Patients With Chronic Hepatitis C Genotype 4

Actual Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

May 31, 2017

Actual Study Completion Date :

May 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SOF/DCV Easy to treat arm: Participants were treated with a dual therapy (SOF and DCV) for 12 weeks. This arm included non-cirrhotic treatment-naïve patients	Drug: (SOF and DCV) Other Names: Daklinza is a trade name of daclatasvir Sovaldi is a trade name of sofosbuvir
Active Comparator: SOF/DCV/RBV + Cirrhosis This difficult-to-treat arm included 111 cirrhotic participants who were treated with a triple therapy (SOF, DCV, and RBV) for 12 weeks.	Drug: (SOF, DCV, and RBV) Other Names: Daklinza is a trade name of daclatasvir Sovaldi is a trade name of sofosbuvir
Active Comparator: SOF/DCV/RBV + Non-Cirrhosis This difficult-to-treat arm included treatment-experienced non-cirrhotic participants (77 participants) who were treated with a triple therapy (SOF, DCV, and RBV) for 12 weeks.	Drug: (SOF, DCV, and RBV) Other Names: Daklinza is a trade name of daclatasvir Sovaldi is a trade name of sofosbuvir

Arm

Intervention/Treatment

Active Comparator: SOF/DCV

Easy to treat arm: Participants were treated with a dual therapy (SOF and DCV) for 12 weeks. This arm included non-cirrhotic treatment-naïve patients

Drug: (SOF and DCV)

Other Names:

Daklinza is a trade name of daclatasvir

Sovaldi is a trade name of sofosbuvir

Active Comparator: SOF/DCV/RBV + Cirrhosis

This difficult-to-treat arm included 111 cirrhotic participants who were treated with a triple therapy (SOF, DCV, and RBV) for 12 weeks.

Drug: (SOF, DCV, and RBV)

Other Names:

Daklinza is a trade name of daclatasvir

Sovaldi is a trade name of sofosbuvir

Active Comparator: SOF/DCV/RBV + Non-Cirrhosis

This difficult-to-treat arm included treatment-experienced non-cirrhotic participants (77 participants) who were treated with a triple therapy (SOF, DCV, and RBV) for 12 weeks.

Drug: (SOF, DCV, and RBV)

Other Names:

Daklinza is a trade name of daclatasvir

Sovaldi is a trade name of sofosbuvir

Outcome Measures

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm SVR12 [12 weeks after last dose]
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level < 15 IU/m 12 weeks after the last dose of drugs.
Number of Participants With Adverse Events in Each Treatment Arm [up for 12 weeks after planned End of Treatment (EOT).]
An adverse event (AE) is defined as any untoward medical occurrence in a participant clinical investigation after administering a pharmaceutical drugs Serious adverse event (SAE) is an event that results in death, life-threatening, requires hospitalization, or significant disability/incapacity

Secondary Outcome Measures

Percentage of Participants With Viral relapse [12 weeks after last dose]
Viral relapse was HCV RNA level ≤ 15 IU/ml at EOT, but detectable HCV RNA level > 15 IU/ml 12 weeks after planned EOT.
Percentage of Participants With On-treatment Virologic Failure [up tp 24 weeks]
On-treatment virologic failure was defined as quantifiable HCV RNA throughout the entire treatment period with HCV RNA greater than 15 IU/ml

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Non-cirrhotic treatment-naïve participants
FIB-4 < 3.25
albumin > 3.5
total bilirubin < 1.2 mg/dl
international normalized ratio (INR) < 1.2
platelet count > 150,000 mm3.
experienced participants who had previously failed treatment with peg-IFN-α-/RBV, SOF/peg-IFN-α +RBV, or SOF/SMV
Naïve cirrhotic participants were confirmed by ultrasonographic features of cirrhosis

Exclusion Criteria:

liver disease of non-HCV etiology
hepatitis B or human immune-deficiency virus (HIV) infection
poorly controlled diabetic (HbA1C > 9) participants
hepatocellular carcinoma
a history of extra-hepatic malignancy within 5 years prior to the study
pregnant or breast feeding
renal disease; serum creatinine > 2.5 mg/dl or eGFR < 30 ml/min
evidence of hepatic decompensation; INR > 1.7, serum albumin < 2.8 g/dl, total bilirubin > 3 mg/dl
blood picture abnormalities such as anemia (hemoglobin concentration of 10 g/dl or less) and thrombocytopenia (platelet count < 50,000 cells/mm3)
major severe illnesses such as congestive heart failure and respiratory failure.