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

Brief Summary:

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 or disease Intervention/treatment Phase
Acute Hepatitis C Human Immunodeficiency Virus Hepatitis C Drug: Grazoprevir/Elbasvir 100mg/50mg Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
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)
Actual Study Start Date : February 2016
Actual Primary Completion Date : April 1, 2018
Actual Study Completion Date : January 11, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment group
Grazoprevir/elbasvir single tablet regimen (100/50mg)
Drug: Grazoprevir/Elbasvir 100mg/50mg
Grazoprevir/Elbasvir 100mg/50mg




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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 <below the limit of detection) is allowed if fibroscan excludes >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.

Information from the National Library of Medicine

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


Locations
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Belgium
Institute of Tropical Medicine Antwerp (ITG)
Antwerpen, Belgium
Netherlands
Erasmus Medical Center (EMC)
Rotterdam, Zuid Holland, Netherlands, 3000 CA
Onze Lieve Vrouwe Gasthuis (OLVG)
Amsterdam, Netherlands
Slotervaart Hospital
Amsterdam, Netherlands
Rijnstate Hospital
Arnhem, Netherlands
University Medical Center Groningen (UMCG)
Groningen, Netherlands
Maastricht University Medical Center (MUMC)
Maastricht, Netherlands
Radbout University Medical Center
Nijmegen, Netherlands
Utrecht Medical University Center (UMCU)
Utrecht, Netherlands
Sponsors and Collaborators
Erasmus Medical Center
Investigators
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Principal Investigator: B Rijnders, PhD Erasmus MC
  Study Documents (Full-Text)

Documents provided by Bart Rijnders, Erasmus Medical Center:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bart Rijnders, Dr., Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02600325    
Other Study ID Numbers: NL2015-003210-24
First Posted: November 9, 2015    Key Record Dates
Results First Posted: July 8, 2019
Last Update Posted: July 8, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Bart Rijnders, Erasmus Medical Center:
Acute Hepatitis C
Human Immunodeficiency virus
Grazoprevir
Elbasvir
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Acquired Immunodeficiency Syndrome
HIV Infections
Hepatitis
Immunologic Deficiency Syndromes
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
MK-5172
Antiviral Agents
Anti-Infective Agents