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Trial record 22 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

Short Duration Therapy of Acute Hepatitis C Genotypes 1 or 4 (SAHIV)

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ClinicalTrials.gov Identifier: NCT02886624
Recruitment Status : Active, not recruiting
First Posted : September 1, 2016
Last Update Posted : November 7, 2018
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Hepatitis C HIV Drug: Grazoprevir/Elbasvir Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Short Duration Therapy of Acute Hepatitis C Genotypes 1 or 4: Efficacy and Tolerability of Grazoprevir 100mg/Elbasvir 50mg During 8 Weeks
Actual Study Start Date : May 24, 2017
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Grazoprevir/Elbasvir
Once-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks
Drug: Grazoprevir/Elbasvir
Once-daily, oral grazoprevir/elbasvir combination therapy at fixed-dose (100mg/50mg) for 8 weeks
Other Name: Zepatier




Primary Outcome Measures :
  1. Sustained virological response 12 weeks post-treatment (SVR12) [ Time Frame: 20 weeks ]
    Undetectable plasma HCV RNA (<12 IU/mL) 12 weeks post-treatment.


Secondary Outcome Measures :
  1. Virological failure [ Time Frame: 20 weeks ]
    Number of patients harboring HCV (NS5A and NS3/4) resistance mutations.

  2. Treatment adherence [ Time Frame: 12 weeks ]
    Average proportion of units used (as declared by the patient) over the total units dispensed (as reported by the pharmacy).

  3. HIV RNA replication [ Time Frame: 20 weeks ]
    Median log HIV RNA at 0 and 20 weeks (in HIV-positive co-infected patients)

  4. CD4 cell count [ Time Frame: 20 weeks ]
    Median CD4+ T cell count at 0 and 20 weeks (in HIV-positive co-infected patients)

  5. Incidence of HCV re-infection [ Time Frame: 56 weeks ]
    Number of patients with positive HCV RNA and a phylogenetically different HCV strain from baseline per hundred person-years of follow-up.



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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. Adult ≥18 years.
  2. 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.
  3. 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).
  4. 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).
  5. Confirmed HIV infection (only for HIV co-infected patients).
  6. Without HIV treatment or with an authorized stable HIV treatment for at least two weeks (only for HIV co-infected patients).
  7. Body weight ≥40 kg and ≤125 kg.
  8. 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.
  9. Informed and signed consent.
  10. Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle).

Exclusion Criteria:

  1. Opportunistic infections (stage C), active or occurred within 6 months prior to baseline.
  2. Primary HIV infection.
  3. Co-infection with Hepatitis B virus (HBsAg-positive) without appropriate treatment (TDF or TAF) for at least 2 weeks.
  4. Confirmed cirrhosis (before acute HCV diagnosis).
  5. Any other causes of acute hepatitis.
  6. Pregnant or breast-feeding women.
  7. Liver transplant recipients.
  8. Evolutive malignancy.
  9. Patients with a history of non-adherence, who will be at risk of being unable to respect the study follow-up timetable.
  10. Patients participating in another clinical trial (with an experimental treatment) or within an exclusion period of a previous clinical trial at screening.
  11. Patients under legal gardianship or incarcerated.
  12. Hemaglobulin <10 g/dL (female) or <11g/dL (male).
  13. Platelet count <50,000/mm3.
  14. Neutrophil count < 750/mm3.
  15. Other antiretroviral drugs than those allowed in the study.
  16. Contra-indications to grazoprevir and/or elbasvir or to any of the excipients listed in the summary of the product characteristics.
  17. Contra-indicated treatment likely to interfere with the study drugs as listed in the summary of the product characteristics.

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): NCT02886624


Locations
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France
CHU de Lyon
Lyon, France, 69317
CHU de Nice
Nice, France, 06200
Hôpital Saint-Antoine
Paris, France, 75012
Hôpital La Pitié-Salpêtrière
Paris, France, 75013
Hôpital Bichat
Paris, France, 75018
Hôpital Tenon
Paris, France, 75020
Sponsors and Collaborators
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Merck Sharp & Dohme Corp.
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
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Principal Investigator: Karine Lacombe, MD, PhD Hôpital Saint-Antoine, Service des maladies infectieuses et tropicales

Publications:

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Responsible Party: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
ClinicalTrials.gov Identifier: NCT02886624     History of Changes
Other Study ID Numbers: IMEA 50
First Posted: September 1, 2016    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Decision by the Scientific Committee is currently pending.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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MK-5172
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents