Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV (DAHHS-2)
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|ClinicalTrials.gov Identifier: NCT02600325|
Recruitment Status : Completed
First Posted : November 9, 2015
Results First Posted : July 8, 2019
Last Update Posted : July 8, 2019
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).
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 or disease||Intervention/treatment||Phase|
|Acute Hepatitis C Human Immunodeficiency Virus Hepatitis C||Drug: Grazoprevir/Elbasvir 100mg/50mg||Phase 3|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||February 2016|
|Actual Primary Completion Date :||April 1, 2018|
|Actual Study Completion Date :||January 11, 2019|
Experimental: Treatment group
Grazoprevir/elbasvir single tablet regimen (100/50mg)
Drug: Grazoprevir/Elbasvir 100mg/50mg
- SVR12 (Reinfection Not Considered Failure) [ Time Frame: 12 weeks ]Sustained viral response (SVR) 12 weeks after the end of therapy in all patients who started treatment in which reinfections are not considered failure
- SVR12 (Reinfection Equals Failure) [ Time Frame: week 12 ]Sustained viral response (SVR) 12 weeks after the end of therapy in all patients who started treatment in which reinfections are considered failure
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02600325
|Institute of Tropical Medicine Antwerp (ITG)|
|Erasmus Medical Center (EMC)|
|Rotterdam, Zuid Holland, Netherlands, 3000 CA|
|Onze Lieve Vrouwe Gasthuis (OLVG)|
|University Medical Center Groningen (UMCG)|
|Maastricht University Medical Center (MUMC)|
|Radbout University Medical Center|
|Utrecht Medical University Center (UMCU)|
|Principal Investigator:||B Rijnders, PhD||Erasmus MC|