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Treatment of Recently Acquired Hepatitis C With the 3D Regimen or G/P (TARGET3D)

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ClinicalTrials.gov Identifier: NCT02634008
Recruitment Status : Recruiting
First Posted : December 17, 2015
Last Update Posted : August 8, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Kirby Institute

Brief Summary:
An open label, multicentre, international pilot study of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin or glecaprevir/pibrentasvir for people with recently acquired hepatitis C virus infection with or without HIV co-infection.

Condition or disease Intervention/treatment Phase
Hepatitis C, Acute Drug: Paritaprevir/ritonavir/ombitasvir Drug: Dasabuvir Drug: Ribavirin Drug: Glecaprevir/pibrentasvir Phase 3

Detailed Description:

The use of a highly potent IFN-sparing drug combination in the setting of recently acquired 1 HCV infection is hypothesised to result in the vast majority of patients achieving SVR. In this setting, it is anticipated that therapy can be shortened relative to that used in established chronic infection. A short course IFN-free strategy is likely to be highly attractive to both patients and clinicians and if proven may further encourage early HCV testing and diagnosis.

In this pilot study, the investigators plan to explore the safety, efficacy and feasibility of the IFN-sparing combination for treatment of recently acquired HCV infection.

Cohort One: paritaprevir/ritonavir/ombitasvir, dasabuvir with/without ribavirin (HCV genotype 1 only) Cohort Two (and Three): glecaprevir/pibrentasvir (HCV genotypes 1-6)


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multicentre, International Pilot Study of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir With or Without Ribavirin or Glecaprevir/Pibrentasvir for People With Recently Acquired Hepatitis C Virus Infection With or Without HIV Co-infection.
Actual Study Start Date : June 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1
Paritaprevir/ritonavir/ombitasvir (75mg/50mg/12.5mg) and dasabuvir (250mg) with or without ribavirin (1000-1200mg) daily taken orally for 8 weeks.
Drug: Paritaprevir/ritonavir/ombitasvir
Other Name: Viekira Pak

Drug: Dasabuvir
Other Name: Viekira Pak

Drug: Ribavirin
Experimental: Cohort 2
Three tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 6 weeks
Drug: Glecaprevir/pibrentasvir
Experimental: Cohort 3
Three tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 4 weeks
Drug: Glecaprevir/pibrentasvir



Primary Outcome Measures :
  1. Proportion of treated subjects (intention-to-treat (ITT) population) demonstrating undetectable hepatitis C virus (HCV) RNA at 12 weeks following treatment (SVR 12). [ Time Frame: 12 weeks post treatment ]

Secondary Outcome Measures :
  1. The proportion of treated subjects overall with ETR, SVR4 and SVR24 defined as undetectable HCV RNA at end of therapy, 4 weeks and 24 weeks post therapy, respectively. [ Time Frame: End of treatment- week 6 or week 8 depending on the study arm; 4 weeks post treatment; 24 weeks post treatment ]
  2. Comparison of ETR, SVR4, SVR12 and SVR24 between those receiving 8 weeks treatment and those receiving 6 weeks treatment. [ Time Frame: End of treatment- week 6 or week 8 depending on the study arm; 4 weeks post treatment; 12 weeks post treatment; 24 weeks post treatment ]
  3. Comparison of adherence between those receiving 8 weeks treatment and those receiving 6 weeks treatment [ Time Frame: Baseline to week 6 or week 8 treatment duration ]
  4. Proportion with early treatment discontinuation [ Time Frame: Baseline through to 6 or 8 weeks depending on the study arm ]
  5. Proportion with adverse events (including serious adverse events) [ Time Frame: Baseline to week 6 or week 8 treatment duration ]
  6. Changes in laboratory parameters, including liver function tests (ALT, AST) and haematological indices (haemoglobin, neutrophil count, platelet count) [ Time Frame: Baseline to week 6 or week 8 treatment duration ]
  7. Emergence of resistance associated variants (RAVs) [ Time Frame: Baseline through to 6 or 8 weeks depending on the study arm ]
  8. HCV reinfection rate [ Time Frame: Week 208 ]
  9. Changes in sexual and injecting drug use behaviour at SVR 12 and end of follow up [ Time Frame: 12 weeks post treatment; week 208 ]
  10. Serum cytokine and ISG expression at baseline and week 4 [ Time Frame: Baseline; week 4 on treatment ]


Information from the National Library of Medicine

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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:

  • Provision of written informed consent;
  • Male and female patients aged 18 years and over;
  • For Cohort One: willing to use two effective methods of contraception during the treatment period and 24 weeks post;
  • For Cohort Two and Three: If female and of childbearing potential, willing to use at least one effective method of contraception during the treatment period and 4 weeks post; women not of childbearing potential include those who are postmenopausal or permanently surgically sterile (no contraception is required for male participants);
  • For Cohort One, Two and Three: Females of child-bearing potential must have a negative pregnancy test at screening and immediately prior to first dose of study drugs;
  • HCV genotype 1 infection at screening (Cohort 1 only);
  • Detectable HCV RNA at screening (>10,000 IU/ml), and in the opinion of the investigator is unlikely to demonstrate spontaneous viral clearance;
  • Absence of cirrhosis, as defined by one of the following:

    • Liver biopsy within 24 months prior to or during screening demonstrating absence of cirrhosis (eg, METAVIR fibrosis score ≤ 3, Ishak fibrosis score ≤ 4); or
    • FibroScan score < 12.5 kPa within ≤ 6 months of screening or during screening period; or
  • Medically stable on the basis of physical examination, medical history and vital signs;
  • Adequate English to provide reliable responses to the study questionnaires;
  • Recently acquired HCV infection (estimated duration of infection ≤12 months) as defined by*:

    1. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii) Documented anti-HCV Ab negative within the 18 months prior to anti-HCV antibody positive result

      OR

    2. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii) Acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the previous 12 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable

      OR

    3. i) First anti-HCV Ab or HCV RNA positive within the previous 6 months and ii) Acute asymptomatic hepatitis (acute rise in ALT> 5 X ULN) within the previous 12 months prior to first positive HCV antibody or HCV RNA and documented normal ALT within the previous 12 months with no othercause of acute hepatitis identifiable (In individuals with a previously high ALT, an acute rise to >3.5 x their previous peak ALT in last 12 months is acceptable)

      OR

    4. 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 or RNA negative and first antibody or HCV RNA positive 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:

      Cohort One:

  • On a stable qualifying ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and a plasma HIV RNA below the limit of detection.

Cohort Two:

• On a stable qualifying ARV regimen for >8 weeks prior to screening visit, with CD4 T cell count >200 cells/mm3 and a plasma HIV RNA below the limit of detection.

OR

• ARV naïve with CD4 T cell count >500 cells/mm3

Exclusion Criteria:

  • Pregnancy/lactation
  • Infection or co-infection with an HCV genotype other than 1 (Cohort 1 only)
  • Subject has current or past clinical evidence of decompensated liver disease, such as ascites, hepatic encephalopathy, oesophageal varices, and/or any of the following screening laboratory results;

    • International Normalized Ration (INR) > 1.5;
    • Patients with a known inherited blood disorder and INR > 1.5 may be enrolled after discussion with the Principal Investigator
    • Serum albumin <3.3 g/dL;
    • Serum total bilirubin >1.8 x upper limit of normal (ULN), unless isolated in subjects with Gilbert's syndrome;
  • 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 active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma);
  • 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;
  • Poorly controlled diabetes mellitus as evidenced by haemoglobin A1c (HbA1c) ≥8.5%;
  • Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months prior to the first dose of study drug
  • Prior treatment failure with an HCV protease inhibitor;
  • Any investigational drug ≤6 weeks prior to the first dose of study drug;
  • Positive test at screening for anti-HAV IgM Ab, anti-HBc IgM Ab or HBsAg;
  • Confirmed presence of hepatocellular carcinoma indicated on imaging techniques such as computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to screening or on an ultrasound performed at screening (a positive ultrasound result will be confirmed with CT scan or MRI);
  • Subject has history of organ transplant that requires chronic immunosuppression

    • Corneal, skin, and hair grafts are allowed;
  • History of severe psychiatric disease that in the opinion of the investigator is unstable enough to compromise treatment adherence;
  • Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis;
  • Prohibited medications and herbal remedies as detailed in section 5.5;
  • Screening laboratory tests showing any of the following abnormal results:

    • Haemoglobin <100 g/L
    • Calculated creatinine clearance <50mL/min
    • Platelets <100,000 cells/mm3
    • Absolute neutrophil count (ANC) <1,500 cells/µL.

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): NCT02634008


Contacts
Contact: Pip Marks +61 2 9385 0886 pmarks@kirby.unsw.edu.au

Locations
Australia, New South Wales
St Vincent's Hospital Recruiting
Sydney, New South Wales, Australia, 2010
Contact: Rebecca Hickey    +61 2 8382 4981    rhickey@stvincents.com.au   
Principal Investigator: Gregory Dore, MBS PhD         
Sub-Investigator: Gail Matthews, MBBS PhD         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Catherine Ferguson    +61 8 8222 5635    catherine.ferguson@health.sa.gov.au   
Principal Investigator: David Shaw         
Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Michelle Hagenauer    03-9282 2261    gaclinresearch@alfred.org.au   
Principal Investigator: Margaret Hellard         
New Zealand
Auckland City Hospital Recruiting
Auckland, Grafton, New Zealand, 1023
Contact: Victoria Oliver    +64 9 307 4949 ext 22917    VictoriaOl@adhb.govt.nz   
Principal Investigator: Ed Gane, MD FRACP         
United Kingdom
Barts and London Recruiting
London, United Kingdom, EC1A 7BE
Contact: Chloe Orkin, MBBCh FRCP       chloe.orkin@bartshealth.nhs.uk   
Principal Investigator: Chloe Orkin, MBBCh FRCP         
Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
Contact: Sanjay Bhagani, MBChB    +44 20 7794 0500 ext 36285    s.bhagani@nhs.net   
Principal Investigator: Sanjay Bhagani, MBChB         
Guy's and St Thomas' Hospital Recruiting
London, United Kingdom, SE1 7EH
Contact: Ranjababu Kulasegeram       gpliaisonlbh@hcahealthcare.co.uk   
Principal Investigator: Ranjababu Kulasegeram         
Chelsea and Westminster Hospital Recruiting
London, United Kingdom, SW10 9NH
Contact: Mark Nelson, MD    +442087465610    m.nelson@ic.ac.uk   
Principal Investigator: Mark Nelson, MD         
St Mary's Hospital Recruiting
London, United Kingdom, W2 1NY
Contact: Graham Cooke       g.cooke@imperial.ac.uk   
Principal Investigator: Graham Cooke         
Sponsors and Collaborators
Kirby Institute
AbbVie
Investigators
Principal Investigator: Gail Matthews, MBBS PhD Kirby Institute

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT02634008     History of Changes
Other Study ID Numbers: VHCRP1502
First Posted: December 17, 2015    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Kirby Institute:
Pangenotypic
Treatment

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Ritonavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors