HIVCOBOC-RGT: Individualized Triple-therapy Using Boceprevir in HIV-positive Patients With Hepatitis C
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
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 Names:
Drug: Boceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Other Names:
|
| 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 Names:
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 Names:
Drug: Boceprevir
800mg three times daily (TID) (e.g. 4x200mg at 6am, 4x200mg at 2pm, 4x200mg at 10pm); orally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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)]
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna | Vienna | Austria | 1090 |
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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HIVCOBOC-RGT
- 2012-005591-33
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration |
|---|---|---|
| Arm/Group Description | All patients will receive 4 weeks of pegylated interferon/ribavirin (PEGIFN/RBV) lead-in. Patients with undetectable hepatitis C virus (HCV)-RNA at treatment week 8 will be treated with 24 weeks of boceprevir (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 | 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 |
| Period Title: Overall Study | ||
| STARTED | 3 | 3 |
| COMPLETED | 2 | 3 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 | Total of all reporting groups |
| Overall Participants | 3 | 3 | 6 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
100%
|
3
100%
|
6
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
1
33.3%
|
1
16.7%
|
| Male |
3
100%
|
2
66.7%
|
5
83.3%
|
Outcome Measures
| Title | Proportion of Subjects With Sustained Virologic Response (SVR12) |
|---|---|
| Description | Defined as HCV-RNA negativity by a sensitive assay |
| Time Frame | Follow-up week 12 (FU12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 3 | 3 |
| Count of Participants [Participants] |
3
100%
|
2
66.7%
|
| Title | Proportions of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | |
| Time Frame | Baseline (BL) to Follow-up week 12 (FU12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 3 | 3 |
| Adverse events (AEs) |
3
100%
|
3
100%
|
| Serious adverse events (SAEs) |
0
0%
|
1
33.3%
|
Adverse Events
| Time Frame | Baseline (BL) to Follow-up week 12 (FU12) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | ||
| Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
| 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/3 (33.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Abscess soft tissue | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| 28 Weeks of Treatment Duration | 48 Weeks of Treatment Duration | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/3 (100%) | 3 | 1/3 (33.3%) | 1 |
| Neutropenia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Platelet count decreased | 3/3 (100%) | 3 | 2/3 (66.7%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
| Vomiting | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
| Diarrhoea | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Glossodynia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Toothache | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| General disorders | ||||
| Fatigue | 3/3 (100%) | 3 | 2/3 (66.7%) | 3 |
| Influenza like illness | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Pyrexia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Immune system disorders | ||||
| Psoriasis | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Nervous system disorders | ||||
| Headache | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 |
| Depression | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Insomnia | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Dyspnoea | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Hair loss | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Markus Peck-Radosavljevic (Principal Investigator) |
|---|---|
| Organization | Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna |
| Phone | +43 1 40400 ext 47440 |
| markus.peck@meduniwien.ac.at |
- HIVCOBOC-RGT
- 2012-005591-33