Hepatitis C, Chronic, HIV
Conditions
Keywords
Boceprevir, HIV/HCV-coinfection, HIV/HCV coinfection, HIV/HCV, Response-guided therapy
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.
Interventions
180mcg once weekly; subcutaneous injection
DRUGRibavirin
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
DRUGBoceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Sponsors
Medical University of Vienna
Markus Peck-Radosavljevic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Sustained Virologic Response (SVR12) | Follow-up week 12 (FU12) | Defined as HCV-RNA negativity by a sensitive assay |
| Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline (BL) to Follow-up week 12 (FU12) | — |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 3 |
| 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
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 | 3 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 |
Outcome results
Primary
Proportion of Subjects With Sustained Virologic Response (SVR12)
Defined as HCV-RNA negativity by a sensitive assay
Time frame: Follow-up week 12 (FU12)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 28 Weeks of Treatment Duration | Proportion of Subjects With Sustained Virologic Response (SVR12) | 3 Participants |
| 48 Weeks of Treatment Duration | Proportion of Subjects With Sustained Virologic Response (SVR12) | 2 Participants |
Primary
Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline (BL) to Follow-up week 12 (FU12)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 28 Weeks of Treatment Duration | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) | 3 Participants |
| 28 Weeks of Treatment Duration | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events (SAEs) | 0 Participants |
| 48 Weeks of Treatment Duration | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) | 3 Participants |
| 48 Weeks of Treatment Duration | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious adverse events (SAEs) | 1 Participants |