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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03250910
Recruitment Status : Completed
First Posted : August 16, 2017
Last Update Posted : December 8, 2017
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Tracking Information
First Submitted Date  ICMJE August 8, 2017
First Posted Date  ICMJE August 16, 2017
Last Update Posted Date December 8, 2017
Actual Study Start Date  ICMJE August 1, 2016
Actual Primary Completion Date July 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2017)
Sustained virologic response [ Time Frame: 24 weeks ]
HCV RNA < LLOQ 12 weeks off therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Generic VEL/SOF With or Without RBV for HIV/HCV Coinfected Patients
Official Title  ICMJE Generic Velpatasvir Plus Sofosbuvir With or Without Ribavirin for the Treatment of Hepatitis C Virus in Patients Coinfected With Human Immunodeficiency Virus
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis C Virus Infection, Response to Therapy of
  • Human Immunodeficiency Virus
Intervention  ICMJE
  • 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.
    Other Name: Sofosvel
  • Drug: 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.
    Other Name: Robatrol
Study Arms  ICMJE
  • Experimental: HIV/HCV compensated liver disease
    Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
    Intervention: Drug: Sofosbuvir and Velpatasvir
  • Experimental: HIV/HCV decompensated liver disease
    Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with 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.
    Interventions:
    • Drug: Sofosbuvir and Velpatasvir
    • Drug: Ribavirin
  • Active Comparator: HCV compensated liver disease
    Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) received a generic version of Sofosbuvir and Velpatasvir fixed-dose combination (Sofosvel®, VEL/SOF 100/400 mg film coated tablet, Beacon Pharmaceuticals Ltd. Mymensingh, Bangladesh) 1 tablet per day for 12 weeks.
    Intervention: Drug: Sofosbuvir and Velpatasvir
  • Active Comparator: HCV decompensated liver disease
    Patients with decompensated cirrhosis (Child-Pugh B or C) received Sofosvel® 1 tablet per day in combination with 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.
    Interventions:
    • Drug: Sofosbuvir and Velpatasvir
    • Drug: Ribavirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 6, 2017)
228
Original Actual Enrollment  ICMJE
 (submitted: August 14, 2017)
178
Actual Study Completion Date  ICMJE October 31, 2017
Actual Primary Completion Date July 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03250910
Other Study ID Numbers  ICMJE 201602026RINC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party National Taiwan University Hospital
Study Sponsor  ICMJE National Taiwan University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chen-Hua Liu, MD National Taiwan University Hospital
PRS Account National Taiwan University Hospital
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP