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MainTitle

Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV (DAHHS-2)

This study is currently recruiting participants. (see Contacts and Locations)

Verified November 2016 by Bart Rijnders, Erasmus Medical Center

Sponsor
Erasmus Medical Center


Information provided by (Responsible Party)
Bart Rijnders, Erasmus Medical Center

ClinicalTrials.gov Identifier
NCT02600325

First received: November 5, 2015
Last updated: November 18, 2016
Last Verified: November 2016
History of Changes
Purpose

Purpose

New and recently EMA/FDA approved direct acting antiviral (DAA) combination therapies cure 95% or more of the patients chronically infected with HCV genotype 1 and 4. Grazoprevir (MK-5172) and elbasvir (MK-8742) combination therapy is such a, albeit not yet EMA/FDA approved combination DAA therapy.

It is likely that the synergistic effect of the host's immune response and antiviral therapy when given during the first 6 months of HCV infection makes antiviral therapy during acute HCV infection more effective. In this study the investigators would like to document that treatment of acute HCV with grazoprevir (MK-5172), elbasvir (MK-8742) is effective and can ben shortened from 12 to 8 weeks for HCV genotype 1 and 4 infection without substantial loss in efficacy.

Study design and intervention:

Prospective open label interventional clinical trial in which 80 acute HCV genotype 1 or 4 patients co-infected with HIV will receive 8 weeks of grazoprevir and elbasvir (a once-daily combination tablet).

Study population:

80 Adult HIV positive patients with an acute HCV genotype 1 or 4 infection from 10 HIV treatment centers in the Netherlands and Belgium will be included.

Primary endpoint: Sustained viral response (SVR) 12 weeks after the end of therapy in ITT study population (=genotype 1 and 4).

Condition Intervention Phase
Acute Hepatitis C
Human Immunodeficiency Virus
Hepatitis C

Drug : Grazoprevir/Elbasvir 100mg/50mg
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Grazoprevir (MK-5172)+ Elbasvir (MK-8742) for the Treatment of Acute Hepatitis C Genotype 1/4. The Dutch Acute HCV in HIV Study (DAHHS-2)

Further study details as provided by Bart Rijnders, Erasmus Medical Center:

Primary Outcome Measures

  • SVR12 [ Time Frame: 24 weeks ]
    Sustained viral response (SVR) 12 weeks after the end of therapy in ITT study population (=genotype 1 and 4).
Secondary Outcome Measures:
  • SVR12 in all genotype 1 infected patients (ITT and mITT) [ Time Frame: 24 weeks ]
    Sustained viral response 12 weeks after the end of therapy in ITT and mITT study population for the genotype 1 subpopulation
  • SVR12 in genotype 4 infected patients (ITT and mITT) [ Time Frame: 24 weeks ]
    Sustained viral response 12 weeks after the end of therapy in ITT and mITT study population for the genotype 4 subpopulation
  • SVR12 in all patients included (mITT) [ Time Frame: 24 weeks ]
    Sustained viral response 12 weeks after the end of therapy in the mITT study population (=genotype 1 and 4)
  • SVR12 in all patients (=genotype 1+4) according to IL28 genotype [ Time Frame: 24 weeks ]
    Sustained viral response 12 weeks after the end of therapy in the IL28B CC versus non-CC genotype
  • SVR24 (mITT and ITT) [ Time Frame: 36 weeks ]
    Sustained viral response 24 weeks after the end of therapy

Estimated Enrollment: 80
Study Start Date: February 2016
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Treatment group
Grazoprevir/elbasvir single tablet regimen (100/50mg)
Drug: Grazoprevir/Elbasvir 100mg/50mg

Grazoprevir/Elbasvir 100mg/50mg

Detailed Description:

Rationale:
Over the last 2 years, the treatment of chronic HCV underwent an enormous change in a positive way. New and recently EMA approved direct acting antiviral (DAA) combination therapies cure as 95% or more of the patients chronically infected with HCV genotype 1 and 4. Grazoprevir (MK-5172) and elbasvir (MK-8742) combination therapy is such a combination DAA therapy. Two recent phase II and 1 phase III clinical trial showed that chronic HCV genotype 1 can be cured with 12 weeks of combination therapy with grazoprevir and elabsvir with a 97% cure in HIV-HCV co-infected patients in the phase III C-Edge co-infection study. However, none of these new HCV therapies have been well studied for the treatment of acute HCV and are therefore not registered for this indication. The only treatment approved for acute HCV is interferon. Interferon based therapy for the treatment of HCV has been shown to be much more effective when given during the acute phase of the HCV infection than at a time when the infection has become chronic. A likely explanation for this difference in success for acute versus chronic HCV therapy is a substantial immune response that is present during the acute phase of HCV infection, but becomes exhausted during chronic infection. This potent immune response is broadly targeted against various HCV epitopes and eradicates approximately 20% of HCV infections within the first 12 to 18 months of infection. However, spontaneous cure of HCV becomes very rare after the first 12 to 18 months of infection due to immune exhaustion. It is likely that the synergistic effect of the host's immune response and antiviral therapy when given during the first 6 months of HCV infection makes direct acting antiviral therapy during acute HCV infection more effective.
Objectives:
To document that treatment of acute HCV with grazoprevir (MK-5172), elbasvir (MK-8742) is effective. To show that, due to the host's immune response at the time of an acute HCV infection, the duration of therapy with grazoprevir (MK-5172) and elbasvir (MK-8742) for acute HCV genotype 1 and 4 infections can be shortened from 12 to 8 weeks without substantial loss in efficacy.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. HIV positive
    2. Acute HCV genotype 1 or 4 infection (≤26 weeks old at the baseline visit)


Exclusion Criteria:
    1. Not on cART and a CD4 <500 at the time of screening
    2. Patients on cART for >6 months with a HIV viral load >400 copies
    3. Disallowed co-medication that cannot be stopped or replaced
    4. History of liver cirrhosis of any etiology. Inclusion of patients with a chronic well-controlled HBV (HBV-DNA F1 fibrosis
    5. Protease inhibitor based and NNRTI based cART regimens are not allowed. Therefore, the
    inability to switch to a HAART regimen consisting of 2 nucleoside/tide reverse transcriptase inhibitors and an allowed third agent which can be raltegravir (Isentress®) 400mg BID, dolutegravir (Tivicay) 50mg QD or rilpivirine 25mg QD.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02600325

Contacts

Contact:   B Rijnders, PhD 31107033510 b.rijnders@erasmusmc.nl

Locations

Belgium
Institute of Tropical Medicine Antwerp (ITG) Recruiting
Antwerpen, Belgium
Contact: Eric Florence, MD
Netherlands
Erasmus Medical Center (EMC) Recruiting
Rotterdam, Zuid Holland, Netherlands, 3000 CA
Contact: Bart J Rijnders, MD, PhD    31107033510    b.rijnders@erasmusmc.nl
Onze Lieve Vrouwe Gasthuis (OLVG) Recruiting
Amsterdam, Netherlands
Slotervaart Hospital Recruiting
Amsterdam, Netherlands
Rijnstate Hospital Recruiting
Arnhem, Netherlands
University Medical Center Groningen (UMCG) Recruiting
Groningen, Netherlands
Maastricht University Medical Center (MUMC) Recruiting
Maastricht, Netherlands
Radbout University Medical Center Recruiting
Nijmegen, Netherlands
Utrecht Medical University Center (UMCU) Recruiting
Utrecht, Netherlands

Sponsors and Collaborators

Erasmus Medical Center

Investigators

Principal Investigator: B Rijnders, PhD Erasmus MC
More Information

More Information


Responsible Party: Bart Rijnders, Dr., Erasmus Medical Center  
ClinicalTrials.gov Identifier: NCT02600325   History of Changes  
Other Study ID Numbers: NL2015-003210-24  
Study First Received: November 5, 2015  
Last Updated: November 18, 2016  

Keywords provided by Bart Rijnders, Erasmus Medical Center:

Acute Hepatitis C
Human Immunodeficiency virus
Grazoprevir
Elbasvir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections

ClinicalTrials.gov processed this data on October 23, 2017
This information is provided by ClinicalTrials.gov.