- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02498015
A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection (D3FEAT)
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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New South Wales
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Sydney, New South Wales, Australia, 2052
- The Kirby Institute, University of New South Wales Australia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Detectable HCV RNA in plasma (>1,000 IU/ml).
- Evidence of positive HCV antibody >6 months prior to screening.
- HCV Genotype 1 infection.
- Recent IDU (previous 6 months) or receiving stable OST (stable dose for >2 weeks).
- Never received treatment for HCV infection.
- 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).
- 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.
- Negative pregnancy test (for women of childbearing potential) within the 24-hour period before the first dose of study drug.
- 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:
- 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.
- Any investigational drug ≤6 weeks before the first dose of study drug.
- HIV infection.
- History or other evidence of decompensated liver disease.
- Neutrophil <1000 cells/mm3 or platelet <50,000 cells/mm3 at screening.
- Serum creatinine >1.5 x upper limit of normal at screening.
- Ongoing severe psychiatric disease as judged by the treating physician.
- Frequent IDU that is judged by the treating physician to compromise treatment safety.
- Hemoglobin <12 g/dL (<7.4 mmol/L) in women or <13 g/dL (<8.1 mmol/L) in men at screening.
- Any exclusion specific to paritaprevir/ritonavir/ombitasvir, dasabuvir or ribavirin.
- Pregnancy/lactation or male subjects whose female partners are pregnant.
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.
- 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.
- Subject has active malignant disease or history of malignant disease within the past 5 years (except 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%.
- 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.
- Prohibited medications and herbal remedies as detailed in the study protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
The "3D" regimen contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg)
once daily, dasabuvir 250mg twice daily for genotype 1b without cirrhosis.
Other Names:
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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.
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment (SVR12)
Time Frame: 12 weeks post treatment
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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.
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12 weeks post treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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To evaluate the proportion of participants with undetectable HCV RNA after receiving 2 weeks of "3D" regimen with or without ribavirin.
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2 weeks following the initiation of treatment
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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
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To evaluate the proportion of participants with undetectable HCV RNA after receiving 4 weeks of "3D" regimen with or without ribavirin.
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4 weeks following the initiation of treatment
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The proportion of participants with undetectable HCV RNA at the end of treatment - week 12
Time Frame: End of treatment week 12
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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.
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End of treatment week 12
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The proportion of participants with undetectable HCV RNA at 24 weeks post end of treatment (SVR24)
Time Frame: 24 weeks post treatment
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To evaluate the proportion of participants with undetectable HCV RNA 24 weeks (SVR24) post end of treatment.
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24 weeks post treatment
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Treatment adherence
Time Frame: Baseline to week 12
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To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation).
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Baseline to week 12
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Association between adherence and response to treatment
Time Frame: Early (0-3 weeks), mid (4-7 weeks), late (8-11 weeks) during treatment
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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.
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Early (0-3 weeks), mid (4-7 weeks), late (8-11 weeks) during treatment
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Safety and tolerability (number and type of adverse events and serious adverse events)
Time Frame: Baseline to week 24 (SVR24)
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To evaluate the number and type of adverse events and serious adverse
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Baseline to week 24 (SVR24)
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Change in injecting drug use and injecting risk behaviour
Time Frame: Baseline to week 12
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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.
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Baseline to week 12
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Change in mental health
Time Frame: Baseline to week 12
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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.
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Baseline to week 12
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Change in health-related quality of life Questionnaire
Time Frame: Baseline to week 12
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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.
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Baseline to week 12
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Impact of mixed HCV infection on treatment response
Time Frame: Baseline to SVR12
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To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response
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Baseline to SVR12
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Change in opioid substitution therapy
Time Frame: Baseline to week 12
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To evaluate the change in OST during treatment (dose and any discontinuation)
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Baseline to week 12
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HCV reinfection rate
Time Frame: Week 108
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To evaluate the rate of HCV reinfection during and following treatment
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Week 108
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Emergence of viral resistance-associated variants (RAVs)
Time Frame: Baseline to week 12
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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.
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Baseline to week 12
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Utility of HCV core antigen testing as a simple method for HCV monitoring
Time Frame: Week 108
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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).
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Week 108
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gregory Dore, MBBS, PhD, Kirby Institute
Publications and helpful links
General Publications
- Cunningham EB, Hajarizadeh B, Amin J, Hellard M, Bruneau J, Feld JJ, Cooper C, Powis J, Litwin AH, Marks P, Dalgard O, Conway B, Moriggia A, Stedman C, Read P, Bruggmann P, Lacombe K, Dunlop A, Applegate TL, Matthews GV, Fraser C, Dore GJ, Grebely J. Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs. Clin Infect Dis. 2021 Apr 26;72(8):1392-1400. doi: 10.1093/cid/ciaa253.
- Artenie AA, Cunningham EB, Dore GJ, Conway B, Dalgard O, Powis J, Bruggmann P, Hellard M, Cooper C, Read P, Feld JJ, Hajarizadeh B, Amin J, Lacombe K, Stedman C, Litwin AH, Marks P, Matthews GV, Quiene S, Erratt A, Bruneau J, Grebely J. Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study. Clin Infect Dis. 2020 May 23;70(11):2369-2376. doi: 10.1093/cid/ciz633.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis
- Hepatitis A
- Hepatitis C
- Hepatitis C, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Ribavirin
Other Study ID Numbers
- VHCRP1405
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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