A Clinical Trial of 16 Weeks of Duration to Evaluate Retreatment With Elbasvir/Grazoprevir Plus Sofosbuvir and Ribavirin in Patients With Chronic Hepatitis C Genotypes 1,4 Who Have Failed to Treat With a Regime Based on an Inhibitor of the NS5A (C-RESCUE)

A Phase III, Open Label, Multicentric Clinical Trial of a Single Arm of 16 Weeks of Duration to Evaluate Retreatment With Elbasvir/Grazoprevir Plus Sofosbuvir and Ribavirin in Patients With Chronic Hepatitis C Genotype 1,4 Who Have Failed to Treat With a Regime Based on an Inhibitor of the NS5A

This is a phase 4 clinical trial to treat patients who have failed to treat with regimen based on an inhibitor of the NS5A

Study Overview

• Status: Withdrawn
• Conditions: HCV
• Intervention / Treatment: Drug: elbasvir/grazoprevir; Drug: Sofosbuvir; Drug: Ribavirin

Detailed Description

The duration of the treatment will be 16 weeks and then will be a security perid with 2 visits (Week 12 post treatment and week 24 post treatment) The study in an open label study with a single arm .

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28031
    • Hospital Infanta Leonor
  • Madrid, Spain, 28007
    • Hospital Univ. Gregorio Marañon
  • Madrid, Spain, 28041
    • Hospita 12 de octubre
  • Madrid, Spain, 28046
    • Hospital Univ. La Paz
  • Madri
    • Madrid, Madri, Spain, 28046
      • Hospital Univ. La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults with chronic HCV genotype 1, 4 infection with or without HIV infection aged 18 years or above
• HCV RNA plasma concentration of at least 1000 IU / mL
• Subjects previously treated with NS5A-based regimens for at least 8 weeks.
• Patients with HCV relapse after receiving a complete treatment with NS5A-based AAD regimen for at least 8 weeks and becoming undetectable at the end of treatment. Relapse is defined as a confirmed HCV RNA detectable upon completion of therapy of A5 based on NS5A against HCV.
• Subjects with compensated hepatic cirrhosis (Child A) could be included.

• For patients with HIV coinfection:

  • Be infected with HIV-1, documented by any rapid HIV test with the corresponding license and confirmed by a Western blot or second antibody test using a method other than the initial rapid HIV and / or I / CIA method or by HIV-1 p24 antigen or viral load of HIV-1 RNA plasma.
  • Be on stable HIV antiretroviral therapy (ART) for at least 4 weeks prior to entry into the study using a dual ITN backbone of tenofovir or abacavir and emtricitabine or lamivudine PLUS raltegravir or dolutegravir or rilpivirine (with CD4 + T cell count> 100 cells / mm 3 and undetectable HIV-1 RNA at baseline. Results from prior analysis will be accepted within 24 weeks prior to study entry).

Exclusion Criteria:

• Subjects with hepatitis other than C or steatosis.
• Subjects previously treated less than 8 weeks with regimens based on NS5A.
• Evidence of previous hepatocellular carcinoma although it has criteria of cure
• Subjects with past or current decompensated liver disease; Only decompensated patients who have received a liver transplant and have not decompensated after transplantation will be included.
• Subjects suspected of clinical or genotypic reinfection of HCV.
• Subject with HCV response regrowth while receiving NS5A-based ADA therapy against HCV. Said regrowth is defined as a confirmation of detectable HCV RNA after achieving undetectable HCV RNA during NS5A-based AADs against HCV.
• Recent history of drug or alcohol abuse.

• Important comorbidities.

  • Pregnant, lactating or non-lactating women Contraceptives, if they are women of childbearing age. Women of childbearing age are defined as those women who have not undergone permanent infertility procedures or who have been amenorrheic for less than 12 months.
  • Subjects with a glomerular filtration rate of less than 30 ml / min.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; 16 weeks treatment with elbasvir/grazoprevir plus sofosbuvir and ribavirina	Drug: elbasvir/grazoprevir; 16 weeks treatment; Other Names: Zepatier; Drug: Sofosbuvir; 16 weeks treatment; Drug: Ribavirin; 16 weeks treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The rate of patients achieved SVR12	Week 12 post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects infected with HCV genotype 1a with reference VARs NS5A / NS3 who achieved RVS12.	To analyze the impact of VARs NS5A/NS3 on RVS12	Week 12 post treatment
The proportion of subjects infected with HCV genotype 1b with reference VARs NS5A / NS3 who achieved RVS12.	Analyze the impact of VARs NS5A/NS3 on RVS12	Week 12 post treatment
The proportion of subjects infected with HCV genotype 4 with reference VARs NS5A /NS3 who achieved RVS12.	Analyze the impact of VARs NS5A/NS3 on RVS12	Week 12 post treatment
The proportion of subjects infected with HCV genotypes 1.4 with reference VARs NS5A /NS3 who achieved RVS24.	Analyze the impact of VARs NS5A/NS3 on RVS24	Week 24 post treatment
The occurrence of Viral resistance variants (VARs) to NS5A or elbasvir, to NS3 or grazoprevir and to NS5B or SOF in patients who did not reach SVR12 after 16 weeks of re-treatment	the occurrence of resistance in patients who did not reach SVR12 after 16 weeks of re-treatment	Week 16
The occurrence of resistance variants (VARs) viral to NS5A or elbasvir, to NS3 or grazoprevir, and to NS5B or SOF in HIV patients included	The impact of VARs NS5A/NS3 on RVS12 The proportion of subjects developing HIV-1 virological failure (HIV RNA> 200 Copies / mL), confirmed in 2 consecutive tests with at least 2 weeks between them.	Week 12 post treatment
The proportion of subjects developing HIV-1 virological failure (HIV RNA> 200 Copies / mL), confirmed in 2 consecutive tests with at least 2 weeks between them	the impact of treatment with EL / BRA plus SOFT and ribavirin in HIV-1 subjects	Week 4, week 8, week 12 and week 16
The proportion of subjects experiencing adverse events of high laboratory values who report as ECI at any time during the study period.	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment
The proportion of subjects with at least one adverse experience	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment
The proportion of subjects with an adverse experience related to medication	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment
The proportion of subjects with a severe adverse experience	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment
The proportion of subjects with a serious adverse experience related to medication	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment
The proportion of subjects with an adverse experience leading to disruption	Adverse events	Week 4, week 8, week 12, week 16, week 12 post-treatment and week 24 post-treatment

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2017
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: April 6, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: June 7, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• 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; Antimetabolites; Sofosbuvir; Ribavirin; Grazoprevir; Elbasvir-grazoprevir drug combination
• Other Study ID Numbers: GESIDA 9516

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