Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C

NCT01925183 | Completed Phase 4 Results DMC

• 2 other identifiers: HIVCOBOC-RGT2012-005591-33
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C, Chronic; HIV

Keywords

Boceprevir; HIV/HCV-coinfection; HIV/HCV coinfection; HIV/HCV; Response-guided therapy

Outcome Measures

Primary Outcomes (2)

• Proportion of Subjects With Sustained Virologic Response (SVR12)

  Defined as HCV-RNA negativity by a sensitive assay

  Follow-up week 12 (FU12)

• Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline (BL) to Follow-up week 12 (FU12)

Study Arms (2)

28 weeks of treatment duration

EXPERIMENTAL

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; Drug: Ribavirin; Drug: Boceprevir

48 weeks of treatment duration

EXPERIMENTAL

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; Drug: Ribavirin; Drug: Boceprevir

Interventions

Pegylated interferon alpha-2a DRUG

180mcg once weekly; subcutaneous injection

Also known as: Pegasys®, Roche

28 weeks of treatment duration; 48 weeks of treatment duration

Ribavirin DRUG

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

Also known as: Copegus®, Roche

28 weeks of treatment duration; 48 weeks of treatment duration

Boceprevir DRUG

800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally

Also known as: Victrelis®, MSD

28 weeks of treatment duration; 48 weeks of treatment duration

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Markus Peck-Radosavljevic: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2a; Ribavirin; N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Markus Peck-Radosavljevic (Principal Investigator)
• Organization: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna

markus.peck@meduniwien.ac.at

+43 1 40400

Study Officials

• Markus Peck-Radosavljevic, MD

  Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice-chairman of the Division of Gastroenterology and Hepatology

Study Record Dates

• First Submitted: August 15, 2013
• First Posted: August 19, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: March 16, 2017
• Results First Posted: February 9, 2017

Record last verified: 2017-02

Locations

AU (1)