Hepatitis C, AcutePhase 3TARGET3DNCT02634008
Treatment of Recently Acquired Hepatitis C With the 3D Regimen or G/P
A Phase 3 study testing Paritaprevir/ritonavir/ombitasvir, Dasabuvir and Ribavirin in people with Hepatitis C, Acute, run by Kirby Institute at 11 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Acute
- What is being tested?
- Paritaprevir/ritonavir/ombitasvir, Dasabuvir and Ribavirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Jun 2016to 30 Apr 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
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- 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*:
- 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
- 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
- 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
- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United Kingdom6 sites
Barts and London
London, EC1A 7BE
Royal Free Hospital
London, NW3 2QG
Guy's and St Thomas' Hospital
London, SE1 7EH
Chelsea and Westminster Hospital
London, SW10 9NH
St Mary's Hospital
London, W2 1NY
Pennine Acute Hospital
Manchester, M8 5RB
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Alfred Hospital
Melbourne, Victoria, 3004
St Vincent's Hospital
Sydney, New South Wales, 2010
New Zealand2 sites
Auckland City Hospital
Auckland, Grafton, 1023
Christchurch Hospital
Christchurch, 8011
About this study
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.
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.
Read the 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)
- Conditions
- Hepatitis C, Acute
- Being tested
- Paritaprevir/ritonavir/ombitasvir, Dasabuvir, Ribavirin, Glecaprevir/pibrentasvir
- Keywords
- Pangenotypic, Treatment
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paritaprevir/ritonavir/ombitasvirDrug
Also called Viekira Pak
DasabuvirDrug
Also called Viekira Pak
RibavirinDrug
Glecaprevir/pibrentasvirDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Paritaprevir/ritonavir/ombitasvir (75mg/50mg/12.5mg) and dasabuvir (250mg) with or without ribavirin (1000-1200mg) daily taken orally for 8 weeks. Receives: Drug: Paritaprevir/ritonavir/ombitasvir; Drug: Dasabuvir; Drug: Ribavirin |
| Cohort 2 | Experimental | Three tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 6 weeks Receives: Drug: Glecaprevir/pibrentasvir |
| Cohort 3 | Experimental | Three tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 4 weeks Receives: Drug: Glecaprevir/pibrentasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of treated subjects (intention-to-treat (ITT) population) demonstrating undetectable hepatitis C virus (HCV) RNA at 12 weeks following treatment (SVR 12).
Measured: 12 weeks post treatment
Secondary outcomes (10)
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.
Measured: End of treatment- week 6 or week 8 depending on the study arm; 4 weeks post treatment; 24 weeks post treatment
Comparison of ETR, SVR4, SVR12 and SVR24 between those receiving 8 weeks treatment and those receiving 6 weeks treatment.
Measured: 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
Comparison of adherence between those receiving 8 weeks treatment and those receiving 6 weeks treatment
Measured: Baseline to week 6 or week 8 treatment duration
Proportion with early treatment discontinuation
Measured: Baseline through to 6 or 8 weeks depending on the study arm
Proportion with adverse events (including serious adverse events)
Measured: Baseline to week 6 or week 8 treatment duration
Changes in laboratory parameters, including liver function tests (ALT, AST) and haematological indices (haemoglobin, neutrophil count, platelet count)
Measured: Baseline to week 6 or week 8 treatment duration
Emergence of resistance associated variants (RAVs)
Measured: Baseline through to 6 or 8 weeks depending on the study arm
HCV reinfection rate
Measured: Week 208
Changes in sexual and injecting drug use behaviour at SVR 12 and end of follow up
Measured: 12 weeks post treatment; week 208
Serum cytokine and ISG expression at baseline and week 4
Measured: Baseline; week 4 on treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study startJun 2016
- Primary completion30 Apr 2021
- Study completion30 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- Gail Matthews, MBBS PhD, Principal investigator, Kirby Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02634008
- Sponsor's protocol ID
- VHCRP1502
- Acronym
- TARGET3D
- Status last verified
- Aug 2022
- First submitted
- 9 Dec 2015
- Last updated
- 22 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Martinello M, Bhagani S, Shaw D, Orkin C, Cooke G, Gane E, Iser D, Ustianowski A, Kulasegaram R, Stedman C, Tu E, Grebely J, Dore GJ, Nelson M, Matthews GV. Glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection: The TARGET3D study. JHEP Rep. 2023 Jul 27;5(10):100867. doi: 10.1016/j.jhepr.2023.100867. eCollection 2023 Oct.
PubMed 37771545
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02634008
- Acronym / sponsor ID
- TARGET3D / VHCRP1502
- Conditions
- Hepatitis C, Acute
- Keywords
- Pangenotypic, Treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Collaborators
- AbbVie
- Study start
- Jun 2016 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Paritaprevir/ritonavir/ombitasvir, Drug: Dasabuvir, Drug: RibavirinParitaprevir/ritonavir/ombitasvir (75mg/50mg/12.5mg) and dasabuvir (250mg) with or without ribavirin (1000-1200mg) daily taken orally for 8 weeks. |
| Cohort 2 | Experimental | Drug: Glecaprevir/pibrentasvirThree tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 6 weeks |
| Cohort 3 | Experimental | Drug: Glecaprevir/pibrentasvirThree tablets of glecaprevir/pibrentasvir (100mg/40mg) daily taken orally for 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- 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;
Key exclusion criteria (26 listed)
- 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;
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paritaprevir/ritonavir/ombitasvirAlso: Viekira Pak | Drug | Cohort 1 |
| DasabuvirAlso: Viekira Pak | Drug | Cohort 1 |
| Ribavirin | Drug | Cohort 1 |
| Glecaprevir/pibrentasvir | Drug | Cohort 2, Cohort 3 |
Primary outcome
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
10 secondary outcomes
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
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
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
Proportion with early treatment discontinuation
Time frame: Baseline through to 6 or 8 weeks depending on the study arm
Proportion with adverse events (including serious adverse events)
Time frame: Baseline to week 6 or week 8 treatment duration
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
Emergence of resistance associated variants (RAVs)
Time frame: Baseline through to 6 or 8 weeks depending on the study arm
HCV reinfection rate
Time frame: Week 208
Changes in sexual and injecting drug use behaviour at SVR 12 and end of follow up
Time frame: 12 weeks post treatment; week 208
Serum cytokine and ISG expression at baseline and week 4
Time frame: Baseline; week 4 on treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Derived from this study: PubMed 37771545Martinello M, Bhagani S, Shaw D, Orkin C, Cooke G, Gane E, Iser D, Ustianowski A, Kulasegaram R, Stedman C, Tu E, Grebely J, Dore GJ, Nelson M, Matthews GV. Glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection: The TARGET3D study. JHEP Rep. 2023 Jul 27;5(10):100867. doi: 10.1016/j.jhepr.2023.100867. eCollection 2023 Oct.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail Matthews, MBBS PhD principal investigator
Kirby Institute
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Paritaprevir/ritonavir/ombitasvir, Dasabuvir and Ribavirin in people with Hepatitis C, Acute, run by Kirby Institute at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United Kingdom, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02634008, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.