Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02625909
Recruitment Status : Active, not recruiting
First Posted : December 9, 2015
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Kirby Institute

Brief Summary:

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 or disease Intervention/treatment Phase
Hepatitis C Drug: SOF/VEL for 6 weeks Drug: SOF/VEL for 12 weeks Phase 3

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
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.
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Interferon

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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)

  6. Toxicity [ 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

  7. 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)

  8. 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

  9. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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:

  1. Antiretroviral (ARV) untreated for >8 weeks preceding screening visit with cluster of differentiation 4 (CD4) T cell count >500 cells/mm3 OR
  2. 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.

  1. 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).
  2. 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
  3. Subject has known cirrhosis
  4. 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
  5. Pregnant or nursing female.
  6. Use of prohibited concomitant medications as described in section 5.2 in the protocol
  7. Chronic use of systemically administered immunosuppressive agents (e.g. prednisone equivalent > 10 mg/day)
  8. Known hypersensitivity to velpatasvir, sofosbuvir or formulation excipients.
  9. 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.
  10. Any investigational drug ≤6 weeks prior to the first dose of study drug.
  11. Previous failure of therapy with sofosbuvir or an non-structural protein 5A (NS5A) inhibitor prior to the first dose of study drug.
  12. Ongoing severe psychiatric disease as judged by the treating physician.
  13. Frequent injecting drug use that is judged by the treating physician to compromise treatment safety.
  14. Inability or unwillingness to provide informed consent or abide by the requirements of the study.

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): NCT02625909


Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114-2621
Australia, New South Wales
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
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Royal Melbourne Hospital
Melbourne, Victoria, Australia, 3050
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, ON M57 2S8
Canada, Quebec
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
Layout table for investigator information
Principal Investigator: Gail V Matthews, MbChB, PhD The Kirby Institute, University of New South Wales Australia, Sydney, New South Wales, Australia, NSW 2052

Layout table for additonal information
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT02625909     History of Changes
Other Study ID Numbers: VHCRP1401
First Posted: December 9, 2015    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: No individual participant data will be shared. The results of the project will be presented at scientific meetings, and published in peer reviewed scientific literature. Sharing of data generated by this project is an essential part of our proposed activities and will be carried out in several different ways. We plan to make our results available to the community of scientists interested in recently acquired hepatitis C, community organisations representing the affected communities and participants. We also welcome collaboration with others who could make use of data and samples.

Layout table for additional information
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:
Layout table for MeSH terms
Hepatitis
Hepatitis A
Hepatitis C
Coinfection
HIV Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Infection
Parasitic Diseases
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Interferons
Sofosbuvir
Velpatasvir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents