A Phase III, Multi-center, Open-label Trial to Investigate the Impact of a Treat, Counsel and Cure Strategy in Men Who Have Sex With Men With Hepatitis C Infection in the Swiss HIV Cohort Study
Overview
- Phase
- Phase 3
- Intervention
- grazoprevir/elbasvir, ribavirin
- Conditions
- Hepatitis C
- Sponsor
- University of Zurich
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Virological efficacy of grazoprevir/elbasvir ±ribavirin: SVR rates at week 12 after treatment stop.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The investigators aim at investigating the efficacy of grazoprevir/elbasvir ±ribavirin in HIV-positive MSM participating in the SHCS in a broader setting of coinfected MSM. The study pursues a comprehensive approach of a treat, counsel and cure strategy exploring the impact of such a strategy in a representative HIV/HCV-coinfected MSM population. This study is a nested project of the Swiss HIV Cohort Study entitled "The Swiss HCVree Trial".
Detailed Description
The prevalence of hepatitis C virus (HCV) infection is increasing in HIV-positive men who have sex with men (MSM) participating in the Swiss HIV Cohort Study (SHCS). MSM with high-risk sexual behaviour are recognized to be the main drivers of the current HCV epidemic. However, in Switzerland treatment with the newest available direct acting agents (DAAs) is currently restricted to patients with a METAVIR fibrosis score ≥2 (i.e., patients with beginning or advanced liver fibrosis or cirrhosis) by the federal office of public health due to the tremendous costs of these DAAs. Within the study population (i.e. HIV-infected MSM with a replicating HCV-infection in Switzerland), about 90% of individuals have a METAVIR fibrosis score \<2. As a consequence, HCV therapy with new DAAs is not covered by health insurances for the majority of this population. However, there is evidence that HCV treatment should not be delayed until the development of advanced liver disease. Treating HIV/HCV-coinfected individuals independently of their liver fibrosis score can prevent the development of liver related complications and the transmission of HCV infection. The once daily oral combination regimen grazoprevir/elbasvir was approved by the Food and Drug Administration (FDA) in January 2016 for the treatment of genotype (GT) 1 and 4 HCV infection in mono- and HIV/HCV coinfected patients. In phase III clinical trial, a 12-week course of grazoprevir/elbasvir showed high efficacy with sustained virologic response (SVR) rates of ≥95%, and favourable tolerability. A 16 weeks treatment with grazoprevir/elbasvir in combination with weight-adjusted ribavirin is necessary in GT 1a infected patients with baseline resistance associated variants (RAV's) and GT 4 infected patients with a history of prior failure to HCV-treatment. Grazoprevir/elbasvir has only robust data from phase 2 and 3 clinical trials for GT 1, 4 HCV infections. Of note, GT 1, 4 infections account for \~90% of HCV infections in the MSM population in the SHCS. HCV reinfection remains a concern among MSM, who can be re-exposed to HCV through high-risk sexual behaviours after successful HCV treatment. A recent review shows evidence that behavioural interventions in high risk MSM have the potential to be effective at least in short term reduction of sexual risk behaviours. To date the knowledge about the HCV-specific immune responses during DAA treatment is sparse. An effective adaptive cellular immunity is known to play a crucial role in spontaneous viral eradication after primary infection. The investigators aim at investigating the efficacy of grazoprevir/elbasvir ±ribavirin in HIV-positive MSM participating in the SHCS in a broader setting of coinfected MSM. The study pursues a comprehensive approach of a treat, counsel and cure strategy exploring the impact of such a strategy in a representative HIV/HCV-coinfected MSM population. This study is a nested project of the Swiss HIV Cohort Study entitled "The Swiss HCVree Trial".
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed consent documented by signature
- •Participation in the SHCS
- •Male individual ≥18 years old
- •Homosexual or bisexual preference/transmission mode according to the SHCS entry state and/or in the opinion of the study physician.
- •Replicating HCV infection (i.e., positive HCV-RNA-test).
- •HCV GT 1 and/or 4 infection.
Exclusion Criteria
- •Contraindications to grazoprevir/elbasvir and ribavirin due to significant drug-drug interactions (DDI) (e.g., HIV protease inhibitors) according to the Liverpool drug-interaction data base.
- •Contraindications to grazoprevir/elbasvir and ribavirin, e.g. known hypersensitivity or allergy to the class of drugs or the investigational product.
- •Participant is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures.
- •Inability to follow the study procedures (e.g. language barriers, psychiatric disorders
- •Known or suspected non-adherence to study-procedures.
- •Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study.
- •Enrolment of the investigator, his/her family members, employees and other dependent persons.
- •Participant suffers from clinically significant concomitant diseases (for the detailed list of diseases we refer to the according section of this protocol).
- •Participant has a history of malignancy ≤5 years prior to signing informed consent or is under evaluation for other active or suspected malignancy.
- •Participant has a history of opportunistic infection in the preceding 6 months prior to screening.
Arms & Interventions
Treatment and behavioural intervention:
Treatment intervention: Patients with a replicating GT 1 and/or 4 HCV infection without or with cirrhosis will be treated with grazoprevir/elbasvir (100mg/50mg) for 12 weeks. GT 1a infected patients with baseline RAV's and GT 4 infected patients with a history of prior HCV treatment failure without or with cirrhosis will be treated with the same regimen for 16 weeks, in combination with weight-adjusted ribavirin. Behavioural Intervention: Participants with inconsistent condom use with occasional partners will receive the behavioral Intervention and in addition standard of care written and oral information on prevention of HCV reinfection. Study participants with consistent condom use or those reporting inconsistent condom use with occasional partners but not willing to participate in the intervention will receive standard of care written and oral information on prevention of HCV reinfection only
Intervention: grazoprevir/elbasvir, ribavirin
Treatment and behavioural intervention:
Treatment intervention: Patients with a replicating GT 1 and/or 4 HCV infection without or with cirrhosis will be treated with grazoprevir/elbasvir (100mg/50mg) for 12 weeks. GT 1a infected patients with baseline RAV's and GT 4 infected patients with a history of prior HCV treatment failure without or with cirrhosis will be treated with the same regimen for 16 weeks, in combination with weight-adjusted ribavirin. Behavioural Intervention: Participants with inconsistent condom use with occasional partners will receive the behavioral Intervention and in addition standard of care written and oral information on prevention of HCV reinfection. Study participants with consistent condom use or those reporting inconsistent condom use with occasional partners but not willing to participate in the intervention will receive standard of care written and oral information on prevention of HCV reinfection only
Intervention: Behavioural Intervention
Outcomes
Primary Outcomes
Virological efficacy of grazoprevir/elbasvir ±ribavirin: SVR rates at week 12 after treatment stop.
Time Frame: 12 weeks after treatment stopp, i.e. week 24.
The main analysis will be the evaluation of SVR 12 weeks after end of treatment (SVR12). We will determine the proportion of patients with an SVR12 (HCV viral load\< 20 copies per ml) in intention to treat analyses including all patients who have received at least one dose of the study compound. Per protocol analyses will also be performed.
Secondary Outcomes
- Change in condom use before and after the behavioural Intervention(At week 0, week 12, and week 24.)
- Safety of grazoprevir/elbasvir ±ribavirin: frequency of adverse events and serious adverse events.(At week 0, week 4, week 6, week 8, week 12, week 16, and week 24.)
- Change in recreational drug use before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in recreational drug use self-efficacy before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in condom use attitude before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in condom use self-efficacy before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in condom use behaviour before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in recreational drug use attitude before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Change in recreational drug use behaviour before and after the behavioural intervention(At week 0, week 12, and week 24.)
- Barriers to treatment: systematic documentation of exclusion reasons for HCV treatment by patient's questionnaire(At week 0)
- HCV treatment uptake: proportion of potentially eligible MSM participating in this study.(At week 0)
- Identification of presumed places of HCV acquisition and modes of HCV transmission: evaluation of patient's questionnaires(At week 0)
- Assessment of HCV-specific cellular immune response: changes of HCV-specific T-cell functionality by ex vivo fluorescence-activated cell sorting (FACS) before and after DAA therapy(At week 0, and week 24)
- Adherence to HCV treatment: proportion of patients which are adherent to ≥95% of prescribed pills(At week 0, week 4, week 6, week 8, week 12, and week 24.)
- Impact of resistance associated variants: SVR 12 in GT 1a infected individuals stratified by presence of baseline RAV's.(At week 24, i.e. 12 weeks after treament stopp)
- Assessment of HCV-specific cellular immune response: changes of HCV-specific T-cell phenotype by ex vivo fluorescence-activated cell sorting (FACS) before and after DAA therapy(At week 0, and week 24)