Clinical trial NCT01743521: DAA Based Therapy for Recently Acquired Hepatitis C (DARE-C)
Official title: Direct Acting Antiviral (DAA) Based Therapy for Recently Acquired Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
Individualised therapy
Response-guided therapy
Telaprevir
PEG-IFN
Ribavirin
Hepatitis
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2012-12-06
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Provision of written, informed consent.
2. HCV genotype 1 infection
3. Quantifiable HCV RNA at screening and baseline (\>10,000 IU/ml)
4. 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
5. Compensated liver disease (Child-Pugh A)
6. Negative pregnancy test at screening and 24 hours prior to the first dose of study drugs.
7. 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.
8. Subject is judged to be medically stable on the basis of physical examination, medical history and vital signs.
9. 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

Primary outcomes:
measure: SVR12 (Sustain Virological Response, HCV RNA Undetectable 12 Weeks Post-treatment)
timeFrame: 12 weeks post-treatment
Secondary outcomes:
measure: SVR24
timeFrame: 24 weeks post-treatment
measure: Undetectable HCV RNA (ETR)
timeFrame: Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Undetectable HCV RNA (Week 1)
timeFrame: Week 1 of therapy
measure: Undectectable HCV RNA (Week 2)
timeFrame: Week 2 of therapy
measure: Undetectable HCV RNA (Week 3)
timeFrame: Week 3 of therapy
measure: Undetectable HCV RNA (Week 4)
timeFrame: Week 4 of therapy
measure: Decrease in Absolute Neutrophil Count (ANC) ≤0.75
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Decrease in Platelets <50
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Change in Hemoglobin at End of Treatment
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Resistance-associated Variants
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Baseline Resistance-associated Variants
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Plasma Ribavirin Levels
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: CD4 and HIV RNA
timeFrame: Baseline, Wk 8 (Group A), Wk 12 (Group B), Wk 24 (Group C)
measure: Gene IL28B Polymorphism
timeFrame: Baseline
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: Kirby Institute
name: Gail Matthews, MbChB, PhD
role: STUDY_CHAIR
References:
citation: Martinello M, Hellard M, Shaw D, Petoumenos K, Applegate T, Grebely J, Yeung B, Maire L, Iser D, Lloyd A, Thompson A, Sasadeusz J, Haber P, Dore GJ, Matthews GV. Short duration response-guided treatment is effective for most individuals with recent hepatitis C infection: the ATAHC II and DARE-C I studies. Antivir Ther. 2016;21(5):425-34. doi: 10.3851/IMP3035. Epub 2016 Feb 11.