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

Phase 4

Completed

Conditions: Hepatitis C, Chronic

Interventions: Drug: TPV/PEG-IFN/RBV

Registration Number: NCT01743521

Lead Sponsor: Kirby Institute

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A - 8 weeks total therapy	TPV/PEG-IFN/RBV	8 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 2 weeks of therapy
Group B - 12 weeks total therapy	TPV/PEG-IFN/RBV	12 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 4 weeks of therapy
Group C - 24 weeks total therapy	TPV/PEG-IFN/RBV	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

Primary Outcome Measures

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

Secondary Outcome Measures

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