Generic VEL/SOF With or Without RBV for HIV/HCV Coinfected Patients

Human Immunodeficiency Virus Clinical Trial

Official title:

Generic Velpatasvir Plus Sofosbuvir With or Without Ribavirin for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03250910
• Other study ID #: 201602026RINC
• Status: Completed
• Phase: Phase 4
• First received: August 8, 2017
• Last updated: December 6, 2017
• Start date: August 1, 2016
• Est. completion date: October 31, 2017

Study information

• Verified date: December 2017
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) with or without ribavirin (RBV) for the treatment of hepatitis C virus (HCV) in patients with human immunodeficiency virus (HIV) coinfection. We aim to compare the effectiveness and safety of VEL/SOF with and without RBV for 12 weeks in HIV/HCV-coinfected and HCV-monoinfected patients The antiviral responses and the adverse events (AEs) are compare between the two groups. The characteristics potentially related to sustained virologic response 12 weeks off therapy (SVR12) are analyzed.

Description:

Due to the lack of effective vaccination and the shared routes of transmission, hepatitis C virus (HCV) infection remains a challenging co-morbidity in patients with human immunodeficiency virus (HIV) infection. It is estimated that approximately 2.3 million people are coinfected with HIV and HCV (HIV/HCV) in the world. Compared to patients with HCV monoinfection, HIV/HCV-coinfected patients tend to have higher serum HCV viral loads, faster hepatic fibrosis progression, and higher risks of hepatic decompensation. Following the commencement of scale-up antiretroviral therapy (ART) that decreases the HIV-related opportunistic infections and malignancies, the liver-related complications have now become the leading cause of morbidity and mortality in HIV/HCV-coinfected patients. On the other hand, the survival rate is improved if these patients achieve sustained virologic response (SVR) by anti-HCV agents.

On the basis of excellent efficacy and safety, treatment by interferon (IFN)-free direct acting antiviral agents (DAAs) has made a paradigm shift for HCV care. Velpatasvir (VEL) is an HCV non-structural protein 5A (NS5A) inhibitor and sofosbuvir (SOF) is an HCV NS5B nucleotide polymerase inhibitor. Both agents are active against HCV with pan-genotypic potency. A fixed-dose combination of VEL at a daily dosage of 100 mg and SOF at a daily dosage of 400 mg (VEL/SOF) with or without weight-based ribavirin (RBV) has been approved by U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat HCV genotype 1-6 patients with compensated and decompensated liver diseases, respectively. Recently, a phase 3 study of VEL/SOF to treat HCV infection in HIV-coinfected patients reveals that this regimen is safe and provides a high and comparable SVR rate to HCV-monoinfected patients.

Although treatment of HCV by IFN-free DAAs is considered highly efficacious and well tolerated, numerous HCV-infected individuals have limited access to the brand-name agents due to the lack of universal governmental reimbursement or private insurance support. Therefore, allowing the generic version of patented DAAs for HCV through voluntary or compulsory licensing may provide patients with greater access to new HCV treatment, particularly in resource-constrained countries. Regarding the real-world experiences of generic IFN-free DAAs, a recent report from China evaluated the effectiveness of a generic version of ledipasvir (LDV) plus SOF (LDV/SOF) with or without RBV for 8-12 weeks in 192 HCV genotype 1b (HCV-1b) patients. The overall SVR rates were excellent (96.8%-96.9%) and most patients tolerated the treatment well. Based on the encouraging results, we aim to evaluate the effectiveness and safety of a generic version of pan-genotypic VEL/SOF-based therapy for HCV in HIV-coinfected patients, and compare the performance of such a regimen in HCV-monoinfected patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: October 31, 2017
• Est. primary completion date: July 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Age > or = 20 years

• Chronic HCV infection, defined as detectable HCV antibody (anti-HCV; Abbott HCV EIA 2.0, Abbott Laboratories, Abbott Park, Illinois, USA) and quantifiable serum HCV RNA (Cobas TaqMan HCV Test v2.0, Roche Diagnostics GmbH, Mannheim, Germany, lower limit of quantification [LLOQ]: 25 IU/mL) for = 6 months

Exclusion Criteria:

• Chronic kidney disease (CKD) stage = 4,

• Organ transplantation

• Prior DAA exposure

• Refusal to provide written informed consent.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection, Response to Therapy of
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes
• Virus Diseases

Intervention

Drug:
• Sofosbuvir and Velpatasvir
All patients received a generic version of VEL/SOF fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
• Ribavirin
Patients with decompensated cirrhosis (Child-Pugh B or C), received weight-based ribavirin (RBV)(Robatrol®, 200 mg capsule, Genovate Biotechnology Co. Ltd., Hsinchu, Taiwan; 1,200 mg per day if the body weight = 75 kg; 1,000 mg per day if the body weight < 75 mg) for 12 weeks.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital, Yun-Lin Branch	Douliu
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response	HCV RNA < LLOQ 12 weeks off therapy	24 weeks