Acute Hepatitis CPhase 3DAHHS-2NCT02600325
Dutch Acute HCV in HIV Study (DAHHS-2): Grazoprevir/Elbasvir for Acute HCV
A Phase 3 study testing Grazoprevir/Elbasvir 100mg/50mg in people with Acute Hepatitis C and Human Immunodeficiency Virus, run by Erasmus Medical Center at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hepatitis C, Human Immunodeficiency Virus, Hepatitis C
- What is being tested?
- Grazoprevir/Elbasvir 100mg/50mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Feb 2016to 11 Jan 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV positive
- Acute HCV genotype 1 or 4 infection (≤26 weeks old at the baseline visit)
Who cannot join
- Not on cART and a CD4 <500 at the time of screening
- Patients on cART for >6 months with a HIV viral load >400 copies
- Disallowed co-medication that cannot be stopped or replaced
- 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
- 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.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Netherlands8 sites
Onze Lieve Vrouwe Gasthuis (OLVG)
Amsterdam
Slotervaart Hospital
Amsterdam
Rijnstate Hospital
Arnhem
University Medical Center Groningen (UMCG)
Groningen
Maastricht University Medical Center (MUMC)
Maastricht
Radbout University Medical Center
Nijmegen
Erasmus Medical Center (EMC)
Rotterdam, South Holland, 3000 CA
Utrecht Medical University Center (UMCU)
Utrecht
About this study
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)
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.
Read more
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).
Read the 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.
- Conditions
- Acute Hepatitis C, Human Immunodeficiency Virus, Hepatitis C
- Being tested
- Grazoprevir/Elbasvir 100mg/50mg
- Keywords
- Acute Hepatitis C, Human Immunodeficiency virus, Grazoprevir, Elbasvir
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Grazoprevir/Elbasvir 100mg/50mgDrug
Grazoprevir/Elbasvir 100mg/50mg
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Grazoprevir/elbasvir single tablet regimen (100/50mg) Receives: Drug: Grazoprevir/Elbasvir 100mg/50mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
SVR12 (Reinfection Not Considered Failure)
Sustained viral response (SVR) 12 weeks after the end of therapy in all patients who started treatment in which reinfections are not considered failure
Measured: 12 weeks
Secondary outcomes (1)
SVR12 (Reinfection Equals Failure)
Sustained viral response (SVR) 12 weeks after the end of therapy in all patients who started treatment in which reinfections are considered failure
Measured: week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2015 (estimated)
- Study startFeb 2016
- Primary completion1 Apr 2018
- Study completion11 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Hepatitis CStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bart Rijnders, Erasmus Medical Center
- Investigators
- B Rijnders, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02600325
- Sponsor's protocol ID
- NL2015-003210-24
- Acronym
- DAHHS-2
- Status last verified
- Apr 2019
- First submitted
- 5 Nov 2015
- Last updated
- 8 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Popping S, Cuypers L, Claassen MAA, van den Berk GE, De Weggheleire A, Arends JE, Boerekamps A, Molenkamp R, Koopmans MPG, Verbon A, Boucher CAB, Rijnders B, van de Vijver DAMC. Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals. Viruses. 2022 Sep 2;14(9):1953. doi: 10.3390/v14091953.
PubMed 36146760Boerekamps A, De Weggheleire A, van den Berk GE, Lauw FN, Claassen MAA, Posthouwer D, Bierman WF, Hullegie SJ, Popping S, van de Vijver DACM, Dofferhoff ASM, Kootstra GJ, Leyten EM, den Hollander J, van Kasteren ME, Soetekouw R, Ammerlaan HSM, Schinkel J, Florence E, Arends JE, Rijnders BJA. Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial. Lancet Gastroenterol Hepatol. 2019 Apr;4(4):269-277. doi: 10.1016/S2468-1253(18)30414-X. Epub 2019 Jan 17.
PubMed 30660617
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02600325
- Acronym / sponsor ID
- DAHHS-2 / NL2015-003210-24
- Conditions
- Acute Hepatitis C, Human Immunodeficiency Virus, Hepatitis C
- Keywords
- Acute Hepatitis C, Human Immunodeficiency virus, Grazoprevir, Elbasvir
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Feb 2016 (actual)
- Primary completion
- 1 Apr 2018 (actual)
- Study completion
- 11 Jan 2019 (actual)
- First posted
- 9 Nov 2015 (estimated)
- Results
- Posted 8 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: Grazoprevir/Elbasvir 100mg/50mgGrazoprevir/elbasvir single tablet regimen (100/50mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- HIV positive
- Acute HCV genotype 1 or 4 infection (≤26 weeks old at the baseline visit)
Key exclusion criteria (5 listed)
- Not on cART and a CD4 <500 at the time of screening
- Patients on cART for >6 months with a HIV viral load >400 copies
- Disallowed co-medication that cannot be stopped or replaced
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Grazoprevir/Elbasvir 100mg/50mgGrazoprevir/Elbasvir 100mg/50mg | Drug | Treatment group |
Primary outcome
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
1 secondary outcome
SVR12 (Reinfection Equals Failure)
Time frame: week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36146760Popping S, Cuypers L, Claassen MAA, van den Berk GE, De Weggheleire A, Arends JE, Boerekamps A, Molenkamp R, Koopmans MPG, Verbon A, Boucher CAB, Rijnders B, van de Vijver DAMC. Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals. Viruses. 2022 Sep 2;14(9):1953. doi: 10.3390/v14091953.
- Derived from this study: PubMed 30660617Boerekamps A, De Weggheleire A, van den Berk GE, Lauw FN, Claassen MAA, Posthouwer D, Bierman WF, Hullegie SJ, Popping S, van de Vijver DACM, Dofferhoff ASM, Kootstra GJ, Leyten EM, den Hollander J, van Kasteren ME, Soetekouw R, Ammerlaan HSM, Schinkel J, Florence E, Arends JE, Rijnders BJA. Treatment of acute hepatitis C genotypes 1 and 4 with 8 weeks of grazoprevir plus elbasvir (DAHHS2): an open-label, multicentre, single-arm, phase 3b trial. Lancet Gastroenterol Hepatol. 2019 Apr;4(4):269-277. doi: 10.1016/S2468-1253(18)30414-X. Epub 2019 Jan 17.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
B Rijnders, PhD principal investigator
Erasmus Medical Center
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Grazoprevir/Elbasvir 100mg/50mg in people with Acute Hepatitis C and Human Immunodeficiency Virus, run by Erasmus Medical Center at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Netherlands, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SVR12 (Reinfection Not Considered Failure) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02600325, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2019.