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A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection (D3FEAT)

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ClinicalTrials.gov Identifier: NCT02498015
Recruitment Status : Completed
First Posted : July 15, 2015
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Kirby Institute

Brief Summary:
A total of 100 people with chronic HCV and recent injection drug use or recipients of opioid substitution therapy will be enrolled in 5 countries and 21 study sites. Participants with genotype 1a infection or cirrhosis will receive 12 weeks of open-label paritaprevir/ritonavir/ombitasvir and dasabuvir ("3D"), and twice-daily ribavirin. Participants with genotype 1b infection without cirrhosis will receive 12 weeks of open-label "3D". The study consists of a screening phase (6 weeks), treatment phase (12 weeks) and follow-up phase (96 weeks) to evaluate treatment response and reinfection.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: "3D" regimen Drug: "3D" regimen with ribavirin Phase 4

Detailed Description:
A total of 100 people with recent injection drug use or recipients of opioid substitution therapy will be enrolled from drug and alcohol clinics, tertiary liver and infectious diseases clinics and community health centres across Canada, Europe, New Zealand, France, and Australia. This will include at least 30 participants with F3/F4 liver disease. Participants will be considered recent injection drug users if they have used injection drugs in the 6 months prior to consent. Participants receiving stable opioid substitution therapy (stable dose for >2 weeks) will also be included. Patients with frequent drug use that is judged by the treating physician to compromise treatment safety will be excluded. The study drugs consisting of two tablets of the co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, one dasabuvir tablet (250 mg) twice daily, ribavirin (1000 mg) daily in two divided doses (genotype 1a only and/or cirrhosis). Electronic blister packs will be used to improve and monitor treatment adherence. This innovative strategy with the "3D" interferon-free regimen could considerably enhance the capacity to scale-up HCV treatment among PWID, and is therefore being evaluated in this phase IV study within a well-defined PWID population.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IV Open-label, Multicentre, International Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir ±Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection and Recent Injection Drug Use or Receiving Opioid Substitution Therapy
Actual Study Start Date : August 2016
Actual Primary Completion Date : August 2017
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: "3D" regimen
The "3D" regimen contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, and one dasabuvir tablet (250 mg) twice daily for genotype 1b without cirrhosis. Treatment will be 12 weeks.
Drug: "3D" regimen
The "3D" regimen contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg) once daily, dasabuvir 250mg twice daily for genotype 1b without cirrhosis.
Other Name: Viekira pack

Experimental: "3D" regimen with ribavirin
The "3D" regimen with ribavirin contain two tablets of co-formulated paritepravir/ritonavir/ombitasvir (75/50/12.5 mg) once daily, one dasabuvir tablet (250 mg) twice daily, and ribavirin (1000 mg regardless of weight) daily in two divided doses for genotype 1a (with/without) and genotype 1b with cirrhosis. Treatment will be for 12 weeks.
Drug: "3D" regimen with ribavirin
The "3D" regimen with ribavirin contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg) once daily, dasabuvir 250mg twice daily, and ribavirin (1000 mg regardless of weight) daily in two divided doses for genotype 1a and genotype 1b with cirrhosis.
Other Name: Viekira pack with ribavirin




Primary Outcome Measures :
  1. The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) [ Time Frame: 12 weeks post treatment ]
    To evaluate the proportion of participants with undetectable HCV RNA 12 weeks post end of treatment (SVR12) following the "3D" regimen with or without ribavirin for 12 weeks in people with chronic HCV genotype 1 infection.


Secondary Outcome Measures :
  1. The proportion of participants with undetectable HCV RNA at 2 weeks following the initiation of treatment - week 2 [ Time Frame: 2 weeks following the initiation of treatment ]
    To evaluate the proportion of participants with undetectable HCV RNA after receiving 2 weeks of "3D" regimen with or without ribavirin.

  2. The proportion of participants with undetectable HCV RNA at 4 weeks following the initiation of treatment - week 4 [ Time Frame: 4 weeks following the initiation of treatment ]
    To evaluate the proportion of participants with undetectable HCV RNA after receiving 4 weeks of "3D" regimen with or without ribavirin.

  3. The proportion of participants with undetectable HCV RNA at the end of treatment - week 12 [ Time Frame: End of treatment week 12 ]
    To evaluate the proportion of participants with undetectable HCV RNA at the end of treatment after receiving 12 weeks of "3D" regimen with or without ribavirin.

  4. The proportion of participants with undetectable HCV RNA at 24 weeks post end of treatment (SVR24) [ Time Frame: 24 weeks post treatment ]
    To evaluate the proportion of participants with undetectable HCV RNA 24 weeks (SVR24) post end of treatment.

  5. Treatment adherence [ Time Frame: Baseline to week 12 ]
    To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation).

  6. Association between adherence and response to treatment [ Time Frame: Early (0-3 weeks), mid (4-7 weeks), late (8-11 weeks) during treatment ]
    To evaluate the association between adherence and response to treatment [including an evaluation of the impact of early (0-3 weeks), mid (4-7 weeks) and late (8-11 weeks) missed doses on response to treatment]; adherence will be measured via a self report questionnaire and pill count via return of the weekly blister packs. The impact of the number and timing of the missed pills will be evaluated.

  7. Safety and tolerability (number and type of adverse events and serious adverse events) [ Time Frame: Baseline to week 24 (SVR24) ]
    To evaluate the number and type of adverse events and serious adverse

  8. Change in injecting drug use and injecting risk behaviour [ Time Frame: Baseline to week 12 ]
    To evaluate the change in injecting drug use and injecting risk behaviours during and following treatment. Change in injecting drug use and injecting risk behaviour will be measured via a self report behavioural questionnaire completed by participants at baseline, week 4 during treatment, week 8 during treatment and end of treatment.

  9. Change in mental health [ Time Frame: Baseline to week 12 ]
    To evaluate the change in mental health during treatment. Change in mental health will be measured by self report mental health questionnaire (Kessler10) at baseline, week 4 during treatment and end of treatment.

  10. Change in health-related quality of life Questionnaire [ Time Frame: Baseline to week 12 ]
    To evaluate the change in health-related quality of life during treatment. Change in health-related quality of life will be measured by self report questionnaire (EQ-5D) at baseline, week 4 during treatment and end of treatment.

  11. Impact of mixed HCV infection on treatment response [ Time Frame: Baseline to SVR12 ]
    To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response

  12. Change in opioid substitution therapy [ Time Frame: Baseline to week 12 ]
    To evaluate the change in OST during treatment (dose and any discontinuation)

  13. HCV reinfection rate [ Time Frame: Week 108 ]
    To evaluate the rate of HCV reinfection during and following treatment

  14. Emergence of viral resistance-associated variants (RAVs) [ Time Frame: Baseline to week 12 ]
    To evaluate the emergence of viral resistance-associated variants (RAVs). HCV sequencing will be performed on the baseline EDTA plasma samples of all participants at baseline to detect any baseline RAVs and will be preformed on the EDTA plasma samples of the participants who experienced virological failure to detect the emergence of RAVs.

  15. Utility of HCV core antigen testing as a simple method for HCV monitoring [ Time Frame: Week 108 ]
    To evaluate the utility of HCV core antigen testing as a simple method for HCV monitoring including treatment response. HCV RNA will be measured using the HCV core antigen test and then compared to HCV RNA levels measured using standard methods (EDTA plasma samples and Roche TaqMan).



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:

  1. Detectable HCV RNA in plasma (>1,000 IU/ml).
  2. Evidence of positive HCV antibody >6 months prior to screening.
  3. HCV Genotype 1 infection.
  4. Recent IDU (previous 6 months) or receiving stable OST (stable dose for >2 weeks).
  5. Never received treatment for HCV infection.
  6. Compensated liver disease. Enrolment of patients with cirrhosis (FibroScan >14.6 kPa or FIB-4 > 3.25) will be capped to 60% of the total enrolment (maximum 3 per site).
  7. Participants with FibroScan > 12KPa or AFP >50 ng/mL must have abdominal ultrasound or CT scan without evidence of hepatocellular carcinoma within 2 months before screening.
  8. Negative pregnancy test (for women of childbearing potential) within the 24-hour period before the first dose of study drug.
  9. All fertile participants must be using effective contraception during treatment and 24 weeks post treatment (patients treated with ribavirin) or 2 weeks post treatment (patients not treated with ribavirin).

Exclusion criteria:

  1. Any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) ≤6 months before the first dose of study drug.
  2. Any investigational drug ≤6 weeks before the first dose of study drug.
  3. HIV infection.
  4. History or other evidence of decompensated liver disease.
  5. Neutrophil <1000 cells/mm3 or platelet <50,000 cells/mm3 at screening.
  6. Serum creatinine >1.5 x upper limit of normal at screening.
  7. Ongoing severe psychiatric disease as judged by the treating physician.
  8. Frequent IDU that is judged by the treating physician to compromise treatment safety.
  9. Hemoglobin <12 g/dL (<7.4 mmol/L) in women or <13 g/dL (<8.1 mmol/L) in men at screening.
  10. Any exclusion specific to paritaprevir/ritonavir/ombitasvir, dasabuvir or ribavirin.
  11. Pregnancy/lactation or male subjects whose female partners are pregnant.
  12. 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;

    a. International normalised ration (INR) >1.5; i. Patients with a known inherited blood disorder and INR > 1.5 may be enrolled after discussion with the Principal Investigator b. Serum albumin <3.3 g/dL; c. Serum total bilirubin >1.8 x ULN, unless isolated in subjects with Gilbert's syndrome.

  13. Subject shows evidence of significant liver disease in addition to HCV, 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.
  14. Subject has active malignant disease or history of malignant disease within the past 5 years (except treated basal cell carcinoma).
  15. 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.
  16. Poorly controlled diabetes mellitus as evidenced by haemoglobin A1c (HbA1c) ≥8.5%.
  17. Positive test at screening for anti-HAV IgM Ab, anti-HBc IgM Ab or HBsAg.
  18. 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).
  19. Subject has history of organ transplant that requires chronic immunosuppression.
  20. Corneal, skin, and hair grafts are allowed.
  21. History of severe psychiatric disease that in the opinion of the investigator is unstable enough to compromise treatment adherence.
  22. Prohibited medications and herbal remedies as detailed in the study protocol.

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): NCT02498015


Locations
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Australia, New South Wales
The Kirby Institute, University of New South Wales Australia
Sydney, New South Wales, Australia, 2052
Sponsors and Collaborators
Kirby Institute
Investigators
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Principal Investigator: Gregory Dore, MBBS, PhD Kirby Institute

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Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT02498015     History of Changes
Other Study ID Numbers: VHCRP1405
First Posted: July 15, 2015    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
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