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

HIV Clinical Trial

— HIVCOBOC-RGT  

Official title:

Response-guided Triple-therapy Using Boceprevir in Combination With PEGIFN/RBV in HIV/HCV-coinfected Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01925183
• Other study ID #: HIVCOBOC-RGT
• Secondary ID: 2012-005591-33
• Status: Recruiting
• Phase: Phase 4
• First received: August 15, 2013
• Last updated: August 16, 2013
• Start date: August 2013

Study information

• Verified date: August 2013
• Source: Medical University of Vienna
• Contact: Mattias Mandorfer, MD
• Phone: +43 1 40400
• Email: mattias.mandorfer[@]meduniwien.ac.at
• Is FDA regulated: No
• Health authority: Austria: Austrian Medicines and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• HIV

Intervention

Drug:
• Pegylated interferon alpha-2a
180mcg once weekly; subcutaneous injection
• 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
• Boceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally

Locations

Country	Name	City	State
Austria	Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Markus Peck-Radosavljevic	Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR12)	Defined as HCV-RNA negativity by a sensitive assay	Follow-up week 12 (FU12)	No
Primary	Adverse events (AEs) and severe adverse events (SAEs)		Baseline (BL) to Follow-up week 12 (FU12)	Yes
Secondary	Sustained virologic response (SVR24)	Defined as HCV-RNA negativity by a sensitive assay	Follow-up week 24 (FU24)	No
Secondary	Anemia	Grade I: Hb male <12/dL, female <11g/dL; Grade II: Hb <10g/dL; Grade III: Hb <8g/dL; Grade IV: Hb <7g/dL	Baseline (BL) to follow-up at week 12 (FU12)	Yes
Secondary	Thrombocytopenia	Grade I: Platelets <150 G/L; Grade II: Platelets <100 G/L; Grade III: Platelets <50 G/L; Grade IV: Platelets <20 G/L	Baseline (BL) to follow-up 12 (FU12)	Yes
Secondary	Neutropenia	Grade I: absolute neutrophil count (ANC) <1000/µL; Grade II: ANC <750/µL; Grade III: ANC <500/µL; Grade IV: ANC <200/µL	Baseline (BL) to follow-up week 12 (FU12)	Yes
Secondary	Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) analogues use		Baseline (BL) to follow-up week 12 (FU12)	Yes
Secondary	Treatment discontinuation due to AEs	* Patients with undetectable HCV-RNA levels at treatment week 8 (W8).; ** Patients with detectable HCV-RNA levels at treatment week 8 (W8).	Baseline (BL) to treatment week 28*/treatment week 48**	Yes
Secondary	Drop-outs		Baseline (BL) to follow-up week 12 (FU12)	No