ٍٍSofosbuvir/Simeprevir/Daclatasvir/Ribavirin and HCV Genotype 4-infected Egyptian Experienced Participants

A Sofosbuvir-based Quadruple Regimen is Highly Effective in HCV Type 4-infected Egyptian Patients With DAA Treatment Failure

Experienced participants who had HCV GT4 infection were treated with Sofosbuvir/Simeprevir/Daclatasvir/Ribavirin (SOF/SMV/DCV/RBV)

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C Virus Infection
• Intervention / Treatment: Drug: SOF/SMV/DCV/RBV

Detailed Description

Experienced participants, who had chronic infection with HCV GT4 , and failed prior DAA treatments, SOF/DCV (71/92) or SOF/SMV (15/92) or SOF/pegylated interferon/RBV (2/92) or SOF/RBV (4/92) were enrolled in the current study.

In the present study, the regimen used was designed by the combination of triple DAAs with different mechanisms of action and non-overlapping resistance profiles, SOF/SMV/DCV, plus RBV.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Bani Sweif, Egypt
    • Health Administration at Beni-Seuf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Experienced Egyptian participants with HCV GT4 infection who had failed prior DAA treatments [SOF/DCV or SOF/SMV or SOF/pegylated interferon/RBV or SOF/RBV]
• Fibrosis-4 score in non-cirrhotic participants is <1.45-3.25: (None or moderate fibrosis)
• Fibrosis-4 score in cirrhotic participants is >3.25: (Advanced fibrosis or cirrhosis)

Exclusion Criteria:

• HCV coinfected with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• had any liver disease other than chronic HCV GT4 infection.
• had a history of liver decompensation
• serum a-fetoprotein (AFP) > 100 ng/ml
• evidence of hepatocellular carcinoma
• major severe illness such as respiratory, renal, heart failure or autoimmune disease
• non-compliance with treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-Cirrhotic; SOF plus DCV/SMV/RBV regimen was administered to Egyptian non-cirrhotic experienced HCV GT4 participants for 12 weeks	Drug: SOF/SMV/DCV/RBV; SOF was given orally at a dose of 400 mg/day DCV was given orally at a dose of 60 mg/day SMV was given orally at a dose of 150 mg/day. RBV was given in a total daily oral dose of 600 mg/day up to 1,200 mg/day according to the participant's weight and tolerability.; Other Names: Olysio is a trade name of simeprevir; Sovaldi is a trade name of sofosbuvir; Daklinza is a trade name of daclatasvir
Active Comparator: Cirrhotic; SOF plus DCV/SMV/RBV regimen was administered to Egyptian cirrhotic experienced HCV GT4 participants for 12 weeks	Drug: SOF/SMV/DCV/RBV; SOF was given orally at a dose of 400 mg/day DCV was given orally at a dose of 60 mg/day SMV was given orally at a dose of 150 mg/day. RBV was given in a total daily oral dose of 600 mg/day up to 1,200 mg/day according to the participant's weight and tolerability.; Other Names: Olysio is a trade name of simeprevir; Sovaldi is a trade name of sofosbuvir; Daklinza is a trade name of daclatasvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) level < 15 IU/m 12 weeks after the last dose of drugs.	12 weeks after last dose
Number of Participants With Adverse Events in Each Treatment Arm	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	Screening up to 12 weeks after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Viral relapse	Viral relapse was HCV RNA level undetectable at End of Treatment (EOT) (≤ 15 IU/ml), but detectable HCV RNA ( > 15 IU/ml) levels 12 weeks after planned EOT.	Up to 12 weeks after last dose

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Investigators: Principal Investigator: Mohammed Abdel-Gabbar, Ass. Prof, Biochemistry Dep., Faculty of Science, Beni-Suef University, P.O. Box 52621

Publications and helpful links

General Publications

• Abdel-Moneim A, Aboud A, Abdel-Gabbar M, Zanaty MI, Ramadan M. A sofosbuvir-based quadruple regimen is highly effective in HCV type 4-infected Egyptian patients with DAA treatment failure. J Hepatol. 2018 Jun;68(6):1313-1315. doi: 10.1016/j.jhep.2018.03.010. Epub 2018 Apr 3. No abstract available.

Helpful Links

• This link shows the investigation performed in the retreatment with SOF plus DCV/SMV/RBV regimen in EgyptianHCV GT4 participants

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): October 31, 2017
• Study Completion (Actual): October 31, 2017

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 10, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 10, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Simeprevir; Chronic HCV GT4; Sofosbuvir; Daclatasvir; Ribavirin; Experienced
• 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; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protease Inhibitors; Sofosbuvir; Simeprevir
• Other Study ID Numbers: SOF/SMV/DCV/RBV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No