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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02498015




Registration number
NCT02498015
Ethics application status
Date submitted
26/06/2015
Date registered
15/07/2015
Date last updated
13/06/2019

Titles & IDs
Public title
A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection
Scientific 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
Secondary ID [1] 0 0
VHCRP1405
Universal Trial Number (UTN)
Trial acronym
D3FEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - "3D" regimen
Treatment: Drugs - "3D" regimen with ribavirin

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.

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.


Treatment: Drugs: "3D" regimen
The "3D" regimen contain paritaprevir/ritonavir/ombitasvir (75/50/12.5mg) once daily, dasabuvir 250mg twice daily for genotype 1b without cirrhosis.

Treatment: Drugs: "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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The proportion of participants with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) - 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.
Timepoint [1] 0 0
12 weeks post treatment
Secondary outcome [1] 0 0
The proportion of participants with undetectable HCV RNA at 2 weeks following the initiation of treatment - week 2 - To evaluate the proportion of participants with undetectable HCV RNA after receiving 2 weeks of "3D" regimen with or without ribavirin.
Timepoint [1] 0 0
2 weeks following the initiation of treatment
Secondary outcome [2] 0 0
The proportion of participants with undetectable HCV RNA at 4 weeks following the initiation of treatment - week 4 - To evaluate the proportion of participants with undetectable HCV RNA after receiving 4 weeks of "3D" regimen with or without ribavirin.
Timepoint [2] 0 0
4 weeks following the initiation of treatment
Secondary outcome [3] 0 0
The proportion of participants with undetectable HCV RNA at the 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.
Timepoint [3] 0 0
End of treatment week 12
Secondary outcome [4] 0 0
The proportion of participants with undetectable HCV RNA at 24 weeks post end of treatment (SVR24) - To evaluate the proportion of participants with undetectable HCV RNA 24 weeks (SVR24) post end of treatment.
Timepoint [4] 0 0
24 weeks post treatment
Secondary outcome [5] 0 0
Treatment adherence - To evaluate the proportion of participants adherent to treatment (both on-treatment adherence and treatment discontinuation).
Timepoint [5] 0 0
Baseline to week 12
Secondary outcome [6] 0 0
Association between adherence and response to 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.
Timepoint [6] 0 0
Early (0-3 weeks), mid (4-7 weeks), late (8-11 weeks) during treatment
Secondary outcome [7] 0 0
Safety and tolerability (number and type of adverse events and serious adverse events) - To evaluate the number and type of adverse events and serious adverse
Timepoint [7] 0 0
Baseline to week 24 (SVR24)
Secondary outcome [8] 0 0
Change in injecting drug use and injecting risk behaviour - 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.
Timepoint [8] 0 0
Baseline to week 12
Secondary outcome [9] 0 0
Change in mental health - 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.
Timepoint [9] 0 0
Baseline to week 12
Secondary outcome [10] 0 0
Change in health-related quality of life Questionnaire - 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.
Timepoint [10] 0 0
Baseline to week 12
Secondary outcome [11] 0 0
Impact of mixed HCV infection on treatment response - To evaluate the rate of mixed HCV infection at baseline and among those with treatment non-response
Timepoint [11] 0 0
Baseline to SVR12
Secondary outcome [12] 0 0
Change in opioid substitution therapy - To evaluate the change in OST during treatment (dose and any discontinuation)
Timepoint [12] 0 0
Baseline to week 12
Secondary outcome [13] 0 0
HCV reinfection rate - To evaluate the rate of HCV reinfection during and following treatment
Timepoint [13] 0 0
Week 108
Secondary outcome [14] 0 0
Emergence of viral resistance-associated variants (RAVs) - 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.
Timepoint [14] 0 0
Baseline to week 12
Secondary outcome [15] 0 0
Utility of HCV core antigen testing as a simple method for HCV monitoring - 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).
Timepoint [15] 0 0
Week 108

Eligibility
Key inclusion 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).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Kirby Institute, University of New South Wales Australia - Sydney
Recruitment postcode(s) [1] 0 0
2052 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
Kirby Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02498015
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gregory Dore, MBBS, PhD
Address 0 0
Kirby Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications