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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: TPV/PEG-IFN/RBV

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A - 8 weeks total therapy; 8 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 2 weeks of therapy	Drug: TPV/PEG-IFN/RBV; 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.; Other Names: Telaprevir brand name: INCIVO; Ribavirin brand name: COPEGUS; PEG-IFN brand name: PEGASYS
Experimental: Group B - 12 weeks total therapy; 12 weeks total therapy of TPV/PEG-IFN/RBV if undetectable HCV RNA after 4 weeks of therapy	Drug: TPV/PEG-IFN/RBV; 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.; Other Names: Telaprevir brand name: INCIVO; Ribavirin brand name: COPEGUS; PEG-IFN brand name: PEGASYS
Experimental: Group C - 24 weeks total therapy; 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; 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.; Other Names: Telaprevir brand name: INCIVO; Ribavirin brand name: COPEGUS; PEG-IFN brand name: PEGASYS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kirby Institute
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Study Chair: Gail Matthews, MbChB, PhD, Kirby Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 6, 2012

Study Record Updates

• Last Update Posted (Actual): March 29, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis C; Hepatitis; Ribavirin; Telaprevir; PEG-IFN; Individualised therapy; Response-guided therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: VHCRP1102; VX-950HCP4010 (Other Grant/Funding Number: Janssen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO