Clinical Trials

MainTitle

Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in PWID and People With HIV Coinfection. (REACT)

This study is ongoing, but not recruiting participants.
Sponsor
Kirby Institute


Information provided by (Responsible Party)
Kirby Institute
ClinicalTrials.gov Identifier
NCT02625909

First received: December 7, 2015
Last updated: February 18, 2020
Last Verified: February 2020
History of Changes
Purpose

Purpose

The aim of the study is to determine if treatment for recently acquired hepatitis C infection (with or without HIV coinfection) can be shortened when treating with the interferon-free therapy sofosbuvir/velpatasvir (SOF/VEL).

SOF/VEL is a new treatment for hepatitis C called direct acting antiviral which targets the hepatitis C virus replication cycle and has been shown in phase II studies in chronic HCV to be highly effective (SVR12 >95%) when given for 12 weeks.

Data has shown that treatment can be shortened when treating recently acquired HCV with interferon containing treatments. It is not known whether treatment with SOF/VEL can be shortened.

This study aims to find out if treatment for 6 weeks with open-label SOF/VEL is equivalent to treatment for 12 weeks with SOF/VEL in participants with recently acquired hepatitis C infection. The project is a randomised study where both participants and investigators would not find out the treatment duration of the participants until week 6 of treatment.

Condition Intervention Phase
Hepatitis C

Drug : SOF/VEL for 6 weeks
Drug : SOF/VEL for 12 weeks
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Study of Interferon-free Treatment for Recently Acquired Hepatitis C in People Who Inject Drugs and People With HIV Coinfection.

Further study details as provided by Kirby Institute:

Primary Outcome Measures

  • The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection (duration of infection less than or equal to 12 months) [ Time Frame: 12 weeks post treatment ]
    To evaluate the proportion of participants with HCV RNA below the level of quantification at 12 weeks post end of treatment following SOF/VEL for 6 weeks as compared with 12 weeks in people with recent HCV infection less than or equal to 12 months.
Secondary Outcome Measures:
  • The proportion of participants with undetectable HCV RNA at end of treatment [ Time Frame: End of treatment - week 6 of the shortened treatment duration arm, and week 12 of the standard treatment duration arm ]
    To evaluate the proportion of participants with HCV RNA below the level of quantification at end of treatment
  • The proportion of participants with SVR4 (sustained virological response 4 weeks post treatment), defined as undetectable HCV RNA at 4 weeks post treatment [ Time Frame: 4 weeks post end of treatment ]
    To evaluate the proportion of participants with HCV RNA below the level of quantification 4 weeks post treatment
  • The proportion of participants with SVR24 (sustained virological response 24 weeks post treatment), defined as undetectable HCV RNA at 24 weeks post treatment [ Time Frame: 24 weeks post treatment ]
    To evaluate the proportion of participants with HCV RNA below the level of quantification 24 weeks post treatment
  • The proportion of participants with undetectable HCV RNA through two years post treatment [ Time Frame: Termination visit (week 102 for shortened treatment duration arm and week 108 for standard treatment duration arm) ]
    To evaluate the proportion of participants with HCV RNA below the level of quantification through 2 years post treatment
  • Treatment adherence [ Time Frame: Baseline to week 6 (shortened treatment duration arm) or week 12 (standard treatment duration arm) ]
    To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation)
  • Toxicity of treatment [ Time Frame: Baseline through to 4 weeks post treatment (SVR4) ]
    To evaluate the proportion of participants with at least one severe or potentially life threatening (grade 3 or 4) adverse event
  • Early treatment discontinuation [ Time Frame: Baseline through to 6 or 12 weeks depending on the study arm ]
    To evaluate the proportion of participants who discontinue therapy prior to the per-protocol planned end of treatment (6 or 12 weeks depending on the study arm)
  • Emergence of viral resistance associated variants (RAVs) [ Time Frame: Baseline through to 6 or 12 weeks depending on the study arm ]
    To evaluate the emergence of viral resistance-associated variants (RAVs). HCV sequencing will be conducted on the baseline EDTA (ethylenediaminetetraacetic acid) plasma samples of all participants to detect any baseline RAVs and will be conducted on the EDTA plasma samples of the participants who experienced virological relapse or breakthrough to detect the emergence of RAVs
  • HCV reinfection rate [ Time Frame: Week 102 (for the shortened treatment duration arm) or 108 (for the standard treatment duration arm) ]
    To evaluate the rate of HCV reinfection during and up to 48 months following end of treatment

Estimated Enrollment: 250
Study Start Date: March 9, 2017
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: May 30, 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Drug: SOF/VEL for 6 weeks
Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the short treatment duration arm (A) for 6 weeks.
Drug: SOF/VEL for 6 weeks

Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm A (6 weeks short treatment duration).

Other Name: sofosbuvir (Sovaldi)/velpatasvir
Experimental: Drug: SOF/VEL for 12 weeks
Open-label SOF/VEL 400mg/100mg co-formulated tablet once daily will be given to participants who are randomised into the standard treatment duration arm (B) for 12 weeks.
Drug: SOF/VEL for 12 weeks

Open-label SOF/VEL 400mg/100mg once daily to be given to participants randomised to Arm B (12 weeks standard treatment duration).

Other Name: sofosbuvir (Sovaldi)/velpatasvir

Detailed Description:

Globally, 3-4 million new HCV infections are estimated to occur annually. People who inject drugs (PWID) represent one of the groups at highest risk of transmitting and acquiring infection with the majority of new (60%) and existing (80%) infections in developed countries occur in this population with HCV antibody prevalence estimated at 67% (60-80%). HIV-positive men-who-have-sex-with-men (MSM) are another high risk group for HCV acquisition.
Direct acting antivirals (DAA) has changed the treatment landscape for individuals with chronic HCV infection with interferon-free therapy offering high effectiveness and tolerability, even in "difficult-to-treat" populations.
Given the burden of HCV-related disease among PWID and HIV-positive MSM, strategies to enhance HCV assessment, treatment and prevention in these groups are urgently needed. Much of what is known about the timing of treatment initiation, regimen choice and duration of therapy in acute HCV infection comes from small observational studies and randomized controlled (randomly assigned into one or other of the different treatment groups)trials in selected populations with limited data on treatment in PWID and HIV co-infection. With recent rapid advances in HCV treatments, management strategies for acute HCV will evolve rapidly over the next few years.
The REACT study will compare the efficacy and safety of open-label SOF/VEL administered for 6 or 12 weeks in individuals with recent HCV infection. Participants will be randomised into receiving 6 weeks or 12 weeks treatment. Both investigators and participants will be blinded to the treatment duration until week 6 of treatment. The role and activity of DAA regimens in acute HCV infection requires evaluation, with the potential to be given as highly effective, short course interferon-sparing regimens, maximising acceptability to patients, encouraging uptake of treatment, limiting further transmission and preventing progression to chronic liver disease.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • Subjects must meet all of the following inclusion criteria to be eligible to participate in this study:
    1. Participants have voluntarily signed the informed consent form.
    2. 18 years of age or older.
    3. Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the investigator is unlikely to demonstrate spontaneous viral clearance
    4. HCV genotypes 1-6.
    5. HBsAg negative
    6. Compensated liver disease (Child-Pugh A)
    7. Negative pregnancy test at baseline (females of childbearing potential only).
    8. Medically stable on the basis of physical examination, medical history and vital signs
    9. Adequate English to provide reliable responses to the study questionnaires
    10. All fertile males and females must be using effective contraception during treatment and during the 30 days after treatment end.
    11. Recently acquired HCV infection (estimated duration of infection ≤12 months)*

    Recently acquired HCV infection as defined by:

  • A) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Documented anti-HCV Ab negative within the 12 months prior to anti-HCV antibody positive result
    OR
    B) i) First anti-HCV Ab or HCV RNA positive within the previous 3 months and ii) Acute clinical hepatitis [jaundice or alanine aminotransferase (ALT)] > 10 X ULN) within the previous 6 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable
    OR
    C) For cases of recent HCV reinfection the following criteria are required:
    Documented prior HCV antibody positive with HCV RNA negative on at least 2 occasions 6 months apart AND new HCV RNA positive within the previous 6 months
    *Estimated duration of infection based on midpoint between last antibody negative or HCV RNA and first antibody positive or HCV RNA in the case of seroconversion and 6 weeks prior to date of maximum ALT in the case of acute hepatitis.
    If co-infection with HIV is documented, the subject must meet the following criteria:
  • Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with cluster of differentiation 4 (CD4) T cell count >500 cells/mm3 OR
  • On a stable ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and an undetectable plasma HIV RNA level.
    • Suitable ARV include:
      • Tenofovir (TDF) and tenofovir alafenamide (TAF)
      • Emtricitabine (FTC)
      • Rilpivirine
      • Dolutegravir
      • Elvitegravir/cobicistat
    • Contraindicated ARV include:
      • Efavirenz 50% reduction in velpatasvir (GS-5816) exposure
      • Didanosine
      • Zidovudine
      • Tipranavir Other ARV agents may be permissible at the time of study commencement pending further drug-drug interaction studies; please discuss with Study Principal Investigator.

      • Exclusion Criteria:

      • Subjects who meet any of the exclusion criteria are not to be enrolled in this study.
  • History of any of the following:
    1. Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with the participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded.
    2. History of chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
    3. Solid organ transplant
    4. Malignancy within 5 years prior to screening, with exception of specific cancers that may have been cured by surgical resection (basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are also excluded.
    5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
  • Subject shows evidence of significant liver disease in addition to hepatitis C, which may include but is not limited to drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis (NASH), or primary biliary cirrhosis
  • Subject has known cirrhosis
  • Any of the following lab parameters at screening:
    1. Direct bilirubin > 1.5 x ULN
    2. Platelets < 50,000/μL
    3. Creatinine clearance (CLcr) < 60 mL/min
    4. Haemoglobin < 11 g/dL for females ; < 12 g/dL for males
    5. Albumin < 30g/L
  • Pregnant or nursing female.
  • Use of prohibited concomitant medications as described in section 5.2 in the protocol
  • Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day)
  • Known hypersensitivity to velpatasvir, sofosbuvir or formulation excipients.
  • Therapy with any anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug.
  • Any investigational drug ≤6 weeks prior to the first dose of study drug.
  • Previous failure of therapy with sofosbuvir or an non-structural protein 5A (NS5A) inhibitor prior to the first dose of study drug.
  • Ongoing severe psychiatric disease as judged by the treating physician.
  • Frequent injecting drug use that is judged by the treating physician to compromise treatment safety.
  • Inability or unwillingness to provide informed consent or abide by the requirements of the study.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02625909

    Locations

    United States, Massachusetts
    Massachusetts General Hospital
    Boston, Massachusetts, United States, 02114-2621
    Australia
    Kirketon Road Centre
    Sydney, New South Wales, Australia, 1340
    St. Vincent's Hospital
    Sydney, New South Wales, Australia, 2010
    The Kirby Institute, University of New South Wales Australia
    Sydney, New South Wales, Australia, 2052
    Royal Adelaide Hospital
    Adelaide, South Australia, Australia, 5000
    The Alfred Hospital
    Melbourne, Victoria, Australia, 3004
    Royal Melbourne Hospital
    Melbourne, Victoria, Australia, 3050
    Canada
    Toronto General Hospital
    Toronto, Ontario, Canada, ON M57 2S8
    Centre Hospitalier de l' Universite de Montreal
    Montreal, Quebec, Canada, QC H2X 1P1
    Germany
    University Hospital of Bonn
    Bonn, Germany, 53105
    Netherlands
    Academic Medical Centre, University of Amsterdam
    Amsterdam, Netherlands, 1105 AZ
    New Zealand
    Auckland City Hospital
    Auckland, New Zealand, 1142
    Switzerland
    Bern University Hospital
    Bern, Switzerland, 3010
    United Kingdom
    Royal Free Hospital
    London, United Kingdom, NW3 2QG
    Chelsea & Westminster Hospital
    London, United Kingdom, SW10 9NH

    Sponsors and Collaborators

    Kirby Institute

    Investigators

    Principal Investigator: Gail V Matthews, MbChB, PhD The Kirby Institute, University of New South Wales Australia, Sydney, New South Wales, Australia, NSW 2052
    More Information

    More Information


    Responsible Party: Kirby Institute  
    ClinicalTrials.gov Identifier: NCT02625909   History of Changes  
    Other Study ID Numbers: VHCRP1401  
    Study First Received: December 7, 2015  
    Last Updated: February 18, 2020  
    Individual Participant Data    
    Plan to Share IPD: Yes  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: No  
    Product Manufactured in and Exported from the U.S.: No  

    Additional relevant MeSH terms:
    Coinfection
    Hepatitis A
    Hepatitis C
    HIV Infections
    Hepatitis
    Sofosbuvir
    Velpatasvir

    ClinicalTrials.gov processed this data on June 02, 2020
    This information is provided by ClinicalTrials.gov.