Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C (HIVCOBOC-RGT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Medical University of Vienna
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
Markus Peck-Radosavljevic, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01925183
First received: August 15, 2013
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

Response-guided triple-therapy with boceprevir (BOC) in combination with pegylated interferon (PEGIFN) and ribavirin (RBV) is the current standard of care for HIV-negative patients infected with hepatitis C genotype (HCV-GT) 1. In contrast, in HIV-positive patients, a fixed treatment duration of 48 weeks is used.

The aim of this study is to assess efficacy and safety of response-guided triple-therapy with BOC in combination with PEGIFN and RBV in HIV-positive patients. Thus, treatment duration will be individualized based on HCV-RNA negativity at treatment week 8 (W8). All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at W8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks, while patients with detectable HCV-RNA at W8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks.


Condition Intervention Phase
Hepatitis C, Chronic
HIV
Drug: Pegylated interferon alpha-2a
Drug: Ribavirin
Drug: Boceprevir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Sustained virologic response (SVR12) [ Time Frame: Follow-up week 12 (FU12) ] [ Designated as safety issue: No ]
    Defined as HCV-RNA negativity by a sensitive assay

  • Adverse events (AEs) and severe adverse events (SAEs) [ Time Frame: Baseline (BL) to Follow-up week 12 (FU12) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Sustained virologic response (SVR24) [ Time Frame: Follow-up week 24 (FU24) ] [ Designated as safety issue: No ]
    Defined as HCV-RNA negativity by a sensitive assay

  • Anemia [ Time Frame: Baseline (BL) to follow-up at week 12 (FU12) ] [ Designated as safety issue: Yes ]
    Grade I: Hb male <12/dL, female <11g/dL; Grade II: Hb <10g/dL; Grade III: Hb <8g/dL; Grade IV: Hb <7g/dL

  • Thrombocytopenia [ Time Frame: Baseline (BL) to follow-up 12 (FU12) ] [ Designated as safety issue: Yes ]
    Grade I: Platelets <150 G/L; Grade II: Platelets <100 G/L; Grade III: Platelets <50 G/L; Grade IV: Platelets <20 G/L

  • Neutropenia [ Time Frame: Baseline (BL) to follow-up week 12 (FU12) ] [ Designated as safety issue: Yes ]
    Grade I: absolute neutrophil count (ANC) <1000/µL; Grade II: ANC <750/µL; Grade III: ANC <500/µL; Grade IV: ANC <200/µL

  • Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) analogues use [ Time Frame: Baseline (BL) to follow-up week 12 (FU12) ] [ Designated as safety issue: Yes ]
  • Treatment discontinuation due to AEs [ Time Frame: Baseline (BL) to treatment week 28*/treatment week 48** ] [ Designated as safety issue: Yes ]

    * Patients with undetectable HCV-RNA levels at treatment week 8 (W8).

    ** Patients with detectable HCV-RNA levels at treatment week 8 (W8).


  • Drop-outs [ Time Frame: Baseline (BL) to follow-up week 12 (FU12) ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: August 2013
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 28 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with undetectable HCV-RNA at treatment week 8 will be treated with 24 weeks of BOC/PEGIFN/RBV triple-therapy resulting in a total treatment duration of 28 weeks.
Drug: Pegylated interferon alpha-2a
180mcg once weekly; subcutaneous injection
Other Name: Pegasys®, Roche
Drug: Ribavirin
600mg two times daily (BID) (e.g. 3x200mg at 6am, 3x200mg at 6pm) in patients ≥75kg body weight; 2x200mg at 6am and 3x200mg at 6pm in patients <75kg; orally
Other Name: Copegus®, Roche
Drug: Boceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Other Name: Victrelis®, MSD
Experimental: 48 weeks of treatment duration
All patients will receive 4 weeks of PEGIFN/RBV lead-in. Patients with detectable HCV-RNA at treatment week 8 will receive 44 weeks of BOC/PEGIFN/RBV triple-therapy and a total treatment duration of 48 weeks
Drug: Pegylated interferon alpha-2a
180mcg once weekly; subcutaneous injection
Other Name: Pegasys®, Roche
Drug: Ribavirin
600mg two times daily (BID) (e.g. 3x200mg at 6am, 3x200mg at 6pm) in patients ≥75kg body weight; 2x200mg at 6am and 3x200mg at 6pm in patients <75kg; orally
Other Name: Copegus®, Roche
Drug: Boceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Other Name: Victrelis®, MSD

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed HIV infection (anti-HIV1/2 antibody positive).
  • Chronic HCV infection (anti-HCV positive, HCV-RNA detectable for >6 months).
  • HCV-GT 1 infection.
  • Age ≥18 years and ≤65 years.
  • No prior treatment with BOC/PEGIFN/RBV.
  • CD4+ cell count >200 cells/µL.
  • Stable antiretroviral therapy (ART) including tenofovir/emtricitabine (Truvada®, Gilead) and raltegravir (Isentress®, MSD) with HIV-RNA <50 copies/mL.
  • Valid result on transient elastography or liver biopsy within 6 months prior to enrollment.
  • Female patients of childbearing potential must agree to use an effective contraceptive during treatment and for 4 months after treatment has been concluded.
  • Male patients or their female partners must agree to use an effective contraceptive during treatment and for 7 months after treatment has been concluded.

Exclusion Criteria:

  • HCV-GT other than HCV-GT 1.
  • Cirrhotic patients (as defined by METAVIR F4 in liver biopsy or liver stiffness >12.3 kPa) with decompensated liver disease (Child-Pugh stage B/C).
  • Chronic liver diseases other than hepatitis C virus infection (hepatitis B virus infection: HBsAg positivity, nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cystic fibrosis).
  • Significant cardiac disease (ejection fraction <40% at echocardiography).
  • Significant pulmonary disease (COPD stage GOLD III/IV).
  • Significant renal disease (serum creatinine >1.5 mg/dL).
  • Subjects taking medication(s) that is/are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events such as but not limited to, orally administered midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine).
  • Contraindications for boceprevir (Victrelis®, MSD), pegylated interferon alpha-2a (Pegasys®, Roche) or ribavirin (Copegus®, Roche), as listed in section 4.3 of the respective summary of product characteristics (SmPCs).
  • Ongoing alcohol abuse (average daily alcohol consumption >50g).
  • Ongoing illicit drug abuse.
  • Unwillingness to give written informed consent.
  • Pregnancy and breastfeeding.
  • Women wishing to become pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925183

Contacts
Contact: Mattias Mandorfer, MD +43 1 40400 ext 4744 mattias.mandorfer@meduniwien.ac.at

Locations
Austria
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Principal Investigator: Markus Peck-Radosavljevic, MD         
Sponsors and Collaborators
Markus Peck-Radosavljevic
Medical University of Vienna
Investigators
Principal Investigator: Markus Peck-Radosavljevic, MD Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna
  More Information

No publications provided

Responsible Party: Markus Peck-Radosavljevic, Vice-chairman of the Division of Gastroenterology and Hepatology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01925183     History of Changes
Other Study ID Numbers: HIVCOBOC-RGT, 2012-005591-33
Study First Received: August 15, 2013
Last Updated: August 16, 2013
Health Authority: Austria: Austrian Medicines and Medical Devices Agency

Keywords provided by Medical University of Vienna:
Boceprevir
HIV/HCV-coinfection
HIV/HCV coinfection
HIV/HCV
Response-guided therapy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferon-alpha
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 15, 2014