DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C)

Study Overview
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Brief Summary
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To examine the safety and efficacy of response guided triple therapy (PEG-IFN, Ribavirin, Telaprevir) for the treatment of early chronic Hepatitis C Virus (HCV) infection.

Detailed Description
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DARE-C is a prospective open label multi-centre pilot study examining the safety and efficacy of response guided triple therapy (PEG-IFN, Ribavirin and Telaprevir) for the treatment of early chronic HCV genotype 1 infection in individuals with and without HIV infection.

Official Title
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Direct Acting Antiviral (DAA) Based Therapy for Recently Acquired Hepatitis C

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: TPV/PEG-IFN/RBV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written, informed consent. HCV genotype 1 infection Quantifiable HCV RNA at screening and baseline (>10,000 IU/ml) Recent hepatitis C infection with an estimated duration of Infection >6 months and ≤ 18 months defined as A) i) First anti-HCV antibody or HCV RNA positive within the previous 6 months and ii) Documented anti-HCV antibody negative or HCV RNA negative within the 24 months prior to anti-HCV antibody positive result OR B) i) First anti-HCV antibody or HCV RNA positive within the previous 6 months and ii) acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the 12 months prior to first positive HCV antibody or HCV RNA with no other cause of acute hepatitis identifiable Compensated liver disease (Child-Pugh A) Negative pregnancy test at screening and 24 hours prior to the first dose of study drugs. If heterosexually active, a female subject of childbearing potential and a nonvasectomized male subject who has a female partner of childbearing potential must agree to use 2 effective contraceptives from screening onwards until 6 months (female subject) or 7 months (male subject) after RBV therapy has ended. Note: Hormonal contraceptives may be continued but may not be reliable during telaprevir dosing and for 2 months following cessation of telaprevir. Therefore, subjects should agree to use 2 effective non-hormonal methods of contraception during telaprevir combination therapy and for 2 months after the last intake of telaprevir. As of two months after completion of telaprevir hormonal contraceptives can again be used as one of the two required effective methods of birth control. Subject is judged to be medically stable on the basis of physical examination, medical history and vital signs. Adequate English to provide written, informed consent and to provide reliable responses to the study interview Additional inclusion criteria for HIV positive individuals Confirmed HIV infection > 6 months duration CD4 > 200 cells/mm3 and HIV < 50 c/ml on stable antiretroviral therapy (ART) at least 3 months prior to treatment Or CD4 >= 500 cells/mm3 and HIV viral load (VL) < 100,000 not on ART If on ART must be taking a regimen containing an accepted* combination of the following drugs: tenofovir ( TDF), lamivudine ( 3TC), emtricitabine (FTC), efavirenz (EFV), abacavir (ABC), raltegravir (RAL), etravirine (ETV), rilpivirine (RIL), ritonavir boosted atazanavir (r/ATZ) * Combination must be supported by current HIV treatment guidelines Exclusion Criteria: Individuals considered by the study investigators to be unlikely to participate in intensive follow-up and/or unwilling to provide extra blood samples Current injecting drug use (any injecting within previous 4 weeks) Standard exclusions to Pegylated-interferon (PEG-IFN), Ribavirin (RBV) and Telaprevir (TPV) therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - 8 weeks total therapy<br>8 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 2 weeks of therapy | Drug: TPV/PEG-IFN/RBV<br>* Drug Telaprevir (TPV): dosed 1125mg twice daily (given as three 375 mg film-coated tablets) orally, except in the situation where a patient is on efavirenz in which case the dose of telaprevir will be 1125mg three times daily. Drug Ribavirin (RBV): 1000mg or 1200mg p.o daily in split doses (1000mg for patients weighing <75kg and 1200mg for patients weighing ≥ 75kg). Drug PEG-IFN (other name: Pegasys): 180mcg in 0.5ml (pre-filled syringes) administered subcutaneously once weekly.<br>* Other names: PEG-IFN brand name: PEGASYS;|
| Experimental: Group B - 12 weeks total therapy<br>12 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 4 weeks of therapy | Drug: TPV/PEG-IFN/RBV<br>* Drug Telaprevir (TPV): dosed 1125mg twice daily (given as three 375 mg film-coated tablets) orally, except in the situation where a patient is on efavirenz in which case the dose of telaprevir will be 1125mg three times daily. Drug Ribavirin (RBV): 1000mg or 1200mg p.o daily in split doses (1000mg for patients weighing <75kg and 1200mg for patients weighing ≥ 75kg). Drug PEG-IFN (other name: Pegasys): 180mcg in 0.5ml (pre-filled syringes) administered subcutaneously once weekly.<br>* Other names: PEG-IFN brand name: PEGASYS;|
| Experimental: Group C - 24 weeks total therapy<br>24 weeks total therapy - TPV/PEG-IFN/RBV for 12 weeks + PEG-IFN/RBV for 12 weeks if undetectable HCV RNA after 8 weeks of therapy | Drug: TPV/PEG-IFN/RBV<br>* Drug Telaprevir (TPV): dosed 1125mg twice daily (given as three 375 mg film-coated tablets) orally, except in the situation where a patient is on efavirenz in which case the dose of telaprevir will be 1125mg three times daily. Drug Ribavirin (RBV): 1000mg or 1200mg p.o daily in split doses (1000mg for patients weighing <75kg and 1200mg for patients weighing ≥ 75kg). Drug PEG-IFN (other name: Pegasys): 180mcg in 0.5ml (pre-filled syringes) administered subcutaneously once weekly.<br>* Other names: PEG-IFN brand name: PEGASYS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR12 (Sustain Virological Response, HCV RNA Undetectable 12 Weeks Post-treatment) | Proportion of subjects achieving SVR 12 (negative qualitative HCV RNA 12 weeks after therapy completion) | 12 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR24 | To evaluate the proportion of patients with undetectable HCV RNA 24 weeks after therapy completion (SVR24) | 24 weeks post-treatment | 
| Undetectable HCV RNA (ETR) | To evaluate the proportion of patients with undetectable HCV RNA at end of treatment (ETR) | Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Undetectable HCV RNA (Week 1) | To evaluate the proportion of patients with undetectable HCV RNA at week 1 of therapy. | Week 1 of therapy | 
| Undectectable HCV RNA (Week 2) | To evaluate the proportion of patients with undetectable HCV RNA at week 1 of therapy. | Week 2 of therapy | 
| Undetectable HCV RNA (Week 3) | To evaluate the proportion of patients with undetectable HCV RNA at week 3 of therapy. | Week 3 of therapy | 
| Undetectable HCV RNA (Week 4) | To evaluate the proportion of patients with undetectable HCV RNA at week 4 of therapy. | Week 4 of therapy | 
| Decrease in Absolute Neutrophil Count (ANC) ≤0.75 |  | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Decrease in Platelets <50 |  | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Change in Hemoglobin at End of Treatment | To evaluate indicators of toxicity during telaprevir based therapy | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Resistance-associated Variants | To examine the emergence of resistance-associated variants during telaprevir based therapy for early chronic infection | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Baseline Resistance-associated Variants | To correlate the presence and frequency of baseline resistance-associated variants (RAVs) with the response of Telaprevir based therapy for early chronic HCV infection. | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Plasma Ribavirin Levels | To correlate plasma ribavirin levels with treatment outcome and changes in haemoglobin during therapy | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| CD4 and HIV RNA | In HIV positive participants to evaluate changes in CD4 counts and HIV RNA during telaprevir based therapy | Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C) | 
| Gene IL28B Polymorphism | To examine treatment outcome by IL28B polymorphism | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Individualised therapy, Response-guided therapy, Telaprevir, PEG-IFN, Ribavirin, Hepatitis