Acute Hepatitis CPhase 2SAHIVNCT02886624
Short Duration Therapy of Acute Hepatitis C Genotypes 1 or 4
A Phase 2 study testing Grazoprevir/Elbasvir in people with Acute Hepatitis C and HIV, run by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba at 6 sites in France.
Trial summary
The purpose of this study is to assess the rate of sustained virological response (SVR) 12 weeks after 8-week oral treatment with grazoprevir 100mg/elbasvir 50mg (MRK-combo) in patients with acute hepatitis C genotype1 or 4. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hepatitis C, HIV
- What is being tested?
- Grazoprevir/Elbasvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesFrance
- Study dates
- 31 May 2017to 16 Sep 2019
- Phase
- Phase 2
- 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
- Adult ≥18 years.
- A recent acute HCV infection [defined by (i) detectable HCV RNA within 6 months after a negative HCV RNA or HCV serology test OR (ii) detectable HCV RNA and acute clinical hepatitis within 5 months prior to screening visit (ALT ≥250 IU/L with normal ALT within the preceding 8 months OR ALT ≥500 IU/L with either no measured ALT or with abnormal ALT within the preceding 8 months)] or reinfection [defined by documented de novo infection after prior clearance post-treatment (defined by one negative HCV RNA ≥6 months after end of treatment) or spontaneously (defined by two negative HCV RNA a minimum of 6 months apart OR documented infection with a new viral strain, confirmed by phylogenetic or genotypic analysis)] within 5 months prior screening OR (iii) patients having reported a risk factor for HCV contamination (traumatic sexual intercourse, intranasal, rectal or intravenous drug use) ≥6 months AND presenting a negative HCV RNA or HCV serology test within 12 months.
- Infection with HCV genotype 1 or 4 (confirmed at screening visit or by using a previous biological test performed 1 to 4 weeks before week 0).
- Plasma HCV-RNA ≥ 1000 IU/mL (confirmed at screening visit or by using a previous biological test performed 1 to 4 weeks before week 0).
- Confirmed HIV infection (only for HIV co-infected patients).
- Without HIV treatment or with an authorized stable HIV treatment for at least two weeks (only for HIV co-infected patients).
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- Body weight ≥40 kg and ≤125 kg.
- Female patients with child-bearing potential and their heterosexual partners must use adequate contraception from the date of screening until 30 days after administration of the last dose of study drug. Male participants must agree to consistently and correctly use a condom, while their female partner must use adequate contraception from the date of screening until 30 days after administration of the last dose of study drug.
- Informed and signed consent.
- Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle).
Who cannot join
- Opportunistic infections (stage C), active or occurred within 6 months prior to baseline.
- Primary HIV infection.
- Co-infection with Hepatitis B virus (HBsAg-positive) without appropriate treatment (TDF or TAF) for at least 2 weeks.
- Confirmed cirrhosis (before acute HCV diagnosis).
- Any other causes of acute hepatitis.
- Pregnant or breast-feeding women.
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- Liver transplant recipients.
- Evolutive malignancy.
- Patients with a history of non-adherence, who will be at risk of being unable to respect the study follow-up timetable.
- Patients participating in another clinical trial (with an experimental treatment) or within an exclusion period of a previous clinical trial at screening.
- Patients under legal gardianship or incarcerated.
- Hemaglobulin <10 g/dL (female) or <11g/dL (male).
- Platelet count <50,000/mm3.
- Neutrophil count < 750/mm3.
- Other antiretroviral drugs than those allowed in the study.
- Contra-indications to grazoprevir and/or elbasvir or to any of the excipients listed in the summary of the product characteristics.
- Contra-indicated treatment likely to interfere with the study drugs as listed in the summary of the product characteristics.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
CHU de Lyon
Lyon, 69317
CHU de Nice
Nice, 06200
Hôpital Saint-Antoine
Paris, 75012
Hôpital La Pitié-Salpêtrière
Paris, 75013
Hôpital Bichat
Paris, 75018
Hôpital Tenon
Paris, 75020
About this study
Official title: Short Duration Therapy of Acute Hepatitis C Genotypes 1 or 4: Efficacy and Tolerability of Grazoprevir 100mg/Elbasvir 50mg During 8 Weeks
The purpose of this study is to assess the rate of sustained virological response (SVR) 12 weeks after 8-week oral treatment with grazoprevir 100mg/elbasvir 50mg (MRK-combo) in patients with acute hepatitis C genotype1 or 4.
Read the detailed description
Increasing rates of acquisition of HCV in men who have sex with men (MSM) have been reported since 2001 in Western European countries and particularly in France. Observational studies have recently reported that HIV-infected gay and bisexual men with sexually transmitted hepatitis C have shown unexpectedly rapid liver disease progression in a relatively short period of time.
It is therefore admitted that, in the absence of a spontaneous HCV clearance within 3 months of acute HCV infection, treatment should be initiated. Pegylated interferon in combination with weight-adapted ribavirin is still recommended as the treatment of choice for all HCV genotypes in an acute setting. For patients developing a rapid virologic response, treatment duration of 24 weeks is recommended. If antiviral therapy was initiated within 24 weeks after diagnosis, sustained virologic response rates of 60 to 80% have been observed at the price of a high side effects burden.
However, short course therapies with new direct acting antivirals are likely to be safer and more efficient. But their efficacy in acute hepatitis C has still to be established. To date, US- and Europe- based trials are ongoing in this setting with the association of sofosbuvir and ribavirine, sofosbuvir / ledipasvir or sofosbuvir / simeprevir, for a duration of 4, 6, 8 or 12 weeks. Preliminary results are very diverse, with SVR12 ranging from 56% to 95%. MSD has been evaluating the efficacy and safety of a double drug combination (grazoprevir + elbasvir) in HIV-infected patients which exhibits paramount efficacy and excellent tolerance in a diverse range of genotypes, including 1 and 4 HCV strains, which are those mainly encountered in the French acute HCV epidemics in MSM. This association has the potential to be used for short treatment duration especially with regards to the fact that patients will have no fibrosis at the time of treatment initiation. This MRK-combo would therefore be an ideal candidate for treating acute hep C due to GT1 or 4 in a "test and treat" approach in high-risk population such as MSM.
- Conditions
- Acute Hepatitis C, HIV
- Being tested
- Grazoprevir/Elbasvir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Grazoprevir/ElbasvirDrug
Also called Zepatier
Once-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Grazoprevir/Elbasvir | Experimental | Once-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks Receives: Drug: Grazoprevir/Elbasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virological Response 12 Weeks Post-treatment (SVR12)
Undetectable plasma HCV RNA (<12 IU/mL) 12 weeks post-treatment.
Measured: 12 weeks
Secondary outcomes (5)
Virological Failure
Number of patients harboring HCV (NS5A and NS3/4) resistance mutations 12 weeks post treatment
Measured: 12 weeks
Treatment Adherence
Number of patients missing study drug within the last four days during treatment
Measured: 8 weeks
Number of Participants With Undetectable HIV RNA
Number of participants with undetectable HIV RNA at 12 weeks post treatment (in HIV-positive co-infected patients)
Measured: 12 weeks
CD4 Cell Count
CD4+ T cell count at 12 weeks post treatment (in HIV-positive co-infected patients)
Measured: 12 weeks
Incidence of HCV Re-infection
Number of patients with positive HCV RNA 48-weeks post treatment.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2016 (estimated)
- Study start31 May 2017
- Primary completion31 Dec 2018
- Study completion16 Sep 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 (4)Papers the sponsor has linked to this study.
- Other trials for Acute Hepatitis CStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Institut National de la Santé Et de la Recherche Médicale, France
- Responsible party
- Sponsor
- Investigators
- Karine Lacombe, MD, PhD, Principal investigator, Hôpital Saint-Antoine, Service des maladies infectieuses et tropicales
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02886624
- Sponsor's protocol ID
- IMEA 50
- Acronym
- SAHIV
- Status last verified
- Jan 2020
- First submitted
- 29 Aug 2016
- Last updated
- 29 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data are available as IPD. An official request must be made to the Principal Investigator. The request will be reviewed by the Scientific Committee. If approved, data will be exchanged according to European Union General Data Protection Regulation.
Publications
Gambotti L, Batisse D, Colin-de-Verdiere N, Delaroque-Astagneau E, Desenclos JC, Dominguez S, Dupont C, Duval X, Gervais A, Ghosn J, Larsen C, Pol S, Serpaggi J, Simon A, Valantin MA, Velter A; Acute hepatitis C collaborating group. Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004. Euro Surveill. 2005 May;10(5):115-7.
PubMed 16077209Fierer DS, Dieterich DT, Fiel MI, Branch AD, Marks KM, Fusco DN, Hsu R, Smith DM, Fierer J. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis. 2013 Apr;56(7):1038-43. doi: 10.1093/cid/cis1206. Epub 2012 Dec 21.
PubMed 23264364European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel. Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS. 2011 Feb 20;25(4):399-409. doi: 10.1097/QAD.0b013e328343443b. No abstract available.
PubMed 21139491Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, Matthews GV, Saag MS, Zamor PJ, Orkin C, Gress J, Klopfer S, Shaughnessy M, Wahl J, Nguyen BY, Barr E, Platt HL, Robertson MN, Sulkowski M. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015 Aug;2(8):e319-27. doi: 10.1016/S2352-3018(15)00114-9. Epub 2015 Jul 9.
PubMed 26423374
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Duration Therapy of Acute Hepatitis C Genotypes 1 or 4: Efficacy and Tolerability of Grazoprevir 100mg/Elbasvir 50mg During 8 Weeks
- ClinicalTrials.gov ID
- NCT02886624
- Acronym / sponsor ID
- SAHIV / IMEA 50
- Conditions
- Acute Hepatitis C, HIV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'BaUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 31 May 2017 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 16 Sep 2019 (actual)
- First posted
- 1 Sep 2016 (estimated)
- Results
- Posted 29 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the rate of sustained virological response (SVR) 12 weeks after 8-week oral treatment with grazoprevir 100mg/elbasvir 50mg (MRK-combo) in patients with acute hepatitis C genotype1 or 4.
Detailed description
Increasing rates of acquisition of HCV in men who have sex with men (MSM) have been reported since 2001 in Western European countries and particularly in France. Observational studies have recently reported that HIV-infected gay and bisexual men with sexually transmitted hepatitis C have shown unexpectedly rapid liver disease progression in a relatively short period of time.
It is therefore admitted that, in the absence of a spontaneous HCV clearance within 3 months of acute HCV infection, treatment should be initiated. Pegylated interferon in combination with weight-adapted ribavirin is still recommended as the treatment of choice for all HCV genotypes in an acute setting. For patients developing a rapid virologic response, treatment duration of 24 weeks is recommended. If antiviral therapy was initiated within 24 weeks after diagnosis, sustained virologic response rates of 60 to 80% have been observed at the price of a high side effects burden.
However, short course therapies with new direct acting antivirals are likely to be safer and more efficient. But their efficacy in acute hepatitis C has still to be established. To date, US- and Europe- based trials are ongoing in this setting with the association of sofosbuvir and ribavirine, sofosbuvir / ledipasvir or sofosbuvir / simeprevir, for a duration of 4, 6, 8 or 12 weeks. Preliminary results are very diverse, with SVR12 ranging from 56% to 95%. MSD has been evaluating the efficacy and safety of a double drug combination (grazoprevir + elbasvir) in HIV-infected patients which exhibits paramount efficacy and excellent tolerance in a diverse range of genotypes, including 1 and 4 HCV strains, which are those mainly encountered in the French acute HCV epidemics in MSM. This association has the potential to be used for short treatment duration especially with regards to the fact that patients will have no fibrosis at the time of treatment initiation. This MRK-combo would therefore be an ideal candidate for treating acute hep C due to GT1 or 4 in a "test and treat" approach in high-risk population such as MSM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Grazoprevir/Elbasvir | Experimental | Drug: Grazoprevir/ElbasvirOnce-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult ≥18 years.
- A recent acute HCV infection [defined by (i) detectable HCV RNA within 6 months after a negative HCV RNA or HCV serology test OR (ii) detectable HCV RNA and acute clinical hepatitis within 5 months prior to screening visit (ALT ≥250 IU/L with normal ALT within the preceding 8 months OR ALT ≥500 IU/L with either no measured ALT or with abnormal ALT within the preceding 8 months)] or reinfection [defined by documented de novo infection after prior clearance post-treatment (defined by one negative HCV RNA ≥6 months after end of treatment) or spontaneously (defined by two negative HCV RNA a minimum of 6 months apart OR documented infection with a new viral strain, confirmed by phylogenetic or genotypic analysis)] within 5 months prior screening OR (iii) patients having reported a risk factor for HCV contamination (traumatic sexual intercourse, intranasal, rectal or intravenous drug use) ≥6 months AND presenting a negative HCV RNA or HCV serology test within 12 months.
- Infection with HCV genotype 1 or 4 (confirmed at screening visit or by using a previous biological test performed 1 to 4 weeks before week 0).
- Plasma HCV-RNA ≥ 1000 IU/mL (confirmed at screening visit or by using a previous biological test performed 1 to 4 weeks before week 0).
- Confirmed HIV infection (only for HIV co-infected patients).
Key exclusion criteria (17 listed)
- Opportunistic infections (stage C), active or occurred within 6 months prior to baseline.
- Primary HIV infection.
- Co-infection with Hepatitis B virus (HBsAg-positive) without appropriate treatment (TDF or TAF) for at least 2 weeks.
- Confirmed cirrhosis (before acute HCV diagnosis).
- Any other causes of acute hepatitis.
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/ElbasvirAlso: ZepatierOnce-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks | Drug | Grazoprevir/Elbasvir |
Primary outcome
Sustained Virological Response 12 Weeks Post-treatment (SVR12)
Time frame: 12 weeks
Undetectable plasma HCV RNA (<12 IU/mL) 12 weeks post-treatment.
5 secondary outcomes
Virological Failure
Time frame: 12 weeks
Treatment Adherence
Time frame: 8 weeks
Number of Participants With Undetectable HIV RNA
Time frame: 12 weeks
CD4 Cell Count
Time frame: 12 weeks
Incidence of HCV Re-infection
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16077209Gambotti L, Batisse D, Colin-de-Verdiere N, Delaroque-Astagneau E, Desenclos JC, Dominguez S, Dupont C, Duval X, Gervais A, Ghosn J, Larsen C, Pol S, Serpaggi J, Simon A, Valantin MA, Velter A; Acute hepatitis C collaborating group. Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004. Euro Surveill. 2005 May;10(5):115-7.
- Background: PubMed 23264364Fierer DS, Dieterich DT, Fiel MI, Branch AD, Marks KM, Fusco DN, Hsu R, Smith DM, Fierer J. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis. 2013 Apr;56(7):1038-43. doi: 10.1093/cid/cis1206. Epub 2012 Dec 21.
- Background: PubMed 21139491European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel. Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS. 2011 Feb 20;25(4):399-409. doi: 10.1097/QAD.0b013e328343443b. No abstract available.
- Background: PubMed 26423374Rockstroh JK, Nelson M, Katlama C, Lalezari J, Mallolas J, Bloch M, Matthews GV, Saag MS, Zamor PJ, Orkin C, Gress J, Klopfer S, Shaughnessy M, Wahl J, Nguyen BY, Barr E, Platt HL, Robertson MN, Sulkowski M. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015 Aug;2(8):e319-27. doi: 10.1016/S2352-3018(15)00114-9. Epub 2015 Jul 9.
- Individual participant dataSharing planned: Yes. All data are available as IPD. An official request must be made to the Principal Investigator. The request will be reviewed by the Scientific Committee. If approved, data will be exchanged according to European Union General Data Protection Regulation.
Related trials for Acute Hepatitis C
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Proteogenomic Monitoring and Assessment of Liver Transplant Recipients
Liver Transplant, Hepatitis C
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.
Karine Lacombe, MD, PhD principal investigator
Hôpital Saint-Antoine, Service des maladies infectieuses et tropicales
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Grazoprevir/Elbasvir in people with Acute Hepatitis C and HIV, run by Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba at 6 sites in France.
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 10 inclusion and 17 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 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 29 Jan 2020). 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?
Sustained Virological Response 12 Weeks Post-treatment (SVR12) (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 NCT02886624, which also lists 4 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 29 Jan 2020.