Hepatitis C, Human Immunodeficiency Virus
Conditions
Brief summary
Prospective open label proof of concept feasibility interventional clinical trial in which 60 acute HCV genotype 1 patients co-infected with HIV will receive 12 weeks of boceprevir in addition to Standard Of Care Peginterferon + Ribavirin if they show a Rapid Viral Responds at week 4. The primary hypothesis of this study is that the subset of patients with a Rapid Viral Responds after 4 weeks of triple therapy with boceprevir, peginterferon alpha-2b (P) and ribavirin (RVR4) can be successfully treated with a shorter 12-week triple therapy regimen.
Interventions
DRUGBoceprevir
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Onze Lieve Vrouwe Gasthuis
UMC Utrecht
University Medical Center Groningen
Maastricht University Medical Center
Rijnstate Hospital
Slotervaart Hospital
Radboud University Medical Center
Erasmus Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented recent HCV genotype 1 infection (≤26 weeks old at the time of the baseline visit) according to definition mentioned below. 2. Plan to start a Standard Of Care therapy for acute HCV consisting of 24 weeks of Peginterferon + Ribavirin. HCV RNA plasma viral load at screening \>1000 IU/ml. 3. A previously performed HCV RNA plasma measurement can be used for screening if \<4 weeks old. 4. On HAART at the time of screening. 5. Minimum age 18 years.
Exclusion criteria
1. Disallowed co-medication that cannot be stopped or replaced: Several potentially life-threatening drug-drug interactions (DDI) are possible when boceprevir is combined with other drugs. Therefore ALL co-medication, including over-the-counter drugs should be checked for potential DDI with DDI table in the Dutch summary of product characteristics (SPC, appendix A). If the co-medication is not mentioned in the SPC DDI table, www.HCV-druginteractions.org should be used. 2. Contraindications for the use of full dose of peginterferon alpha-2b or ribavirin: neutrophils \<0,75×109/l or thrombocytes \< 100.000×109/l or a Hb \<6.2mmol/L, creatinine clearance \<50ml/min). 3. History of liver cirrhosis or \>F1 fibrosis on fibroscan. Inclusion of patients with a chronic well-controlled HBV (HBV-DNA below the limit of detection) with tenofovir, lamivudine or emtricitabine therapy is allowed if fibroscan excludes \>F1 fibrosis. Fibroscan reports \<2 years old can be used for screening. Fibroscan is not required for other patients at screening. 4. HAART was started \<4 weeks before baseline visit. 5. Inability to switch to a HAART regimen consisting of 2 nucleoside/tide reverse transcriptase inhibitors + Raltegravir (Isentress®) 400mg BID or rilpivirine 25mg QD or atazanavir (Reyataz®) 300mg QD + ritonavir (Norvir®) 100mg QD. 6. Patient that virologically failed HAART in the past
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Viral Response(SVR) 12 Weeks of Follow up After the End of All Therapy for the Rapid Viral Response at Week 4(RVR4) Population. | 12 weeks | The outcome is a number of the patients with an undetectable Hepatitis C Virus (HCV) RNA at week 4 that have an undetectable HCV RNA 12 weeks after end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4). | 12 weeks | The outcome is a number of all patients who started treatment having an undetectable HCV RNA 12 weeks after the end of therapy |
| SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1. | 12 weeks | The number of patients who were undetectable for HCV at week one that had an undetectable HCV RNA load 12 weeks after the end of treatment |
| SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks. | 12 weeks | The number of patients having a undetectable HCV RNA 12 weeks after the end of treatment in the group patients that was treated within 12 week of calculated transmission date. |
| Alterations of Biomarkers by Therapy Induced Viral Eradication: Viral Sequencing, Mutation Analysis, Gene Expression Analysis, and RNA Analysis. | 72 weeks | — |
| Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE. | 72 weeks | only serious adverse events are recorded in this secondary endpoint |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Boceprevir/Peginterferon/Ribavirin Boceprevir with Peginterferon and Ribavirin | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | Boceprevir/Peginterferon/Ribavirin |
|---|---|
| Age, Continuous | 40 years |
| Region of Enrollment Netherlands | 57 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 57 |
| serious Total, serious adverse events | 3 / 57 |
Outcome results
Primary
Sustained Viral Response(SVR) 12 Weeks of Follow up After the End of All Therapy for the Rapid Viral Response at Week 4(RVR4) Population.
The outcome is a number of the patients with an undetectable Hepatitis C Virus (HCV) RNA at week 4 that have an undetectable HCV RNA 12 weeks after end of treatment.
Time frame: 12 weeks
Population: 41 patients had a RVR4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boceprevir, Peginterferon and Ribavirin | Sustained Viral Response(SVR) 12 Weeks of Follow up After the End of All Therapy for the Rapid Viral Response at Week 4(RVR4) Population. | 41 participants |
Secondary
Alterations of Biomarkers by Therapy Induced Viral Eradication: Viral Sequencing, Mutation Analysis, Gene Expression Analysis, and RNA Analysis.
Time frame: 72 weeks
Population: data were not collected during this study
Secondary
Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE.
only serious adverse events are recorded in this secondary endpoint
Time frame: 72 weeks
Population: 57 patients started treatment and were at risk
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boceprevir, Peginterferon and Ribavirin | Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE. | 3 participants |
Secondary
SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks.
The number of patients having a undetectable HCV RNA 12 weeks after the end of treatment in the group patients that was treated within 12 week of calculated transmission date.
Time frame: 12 weeks
Population: 5 patients were treated within 12 weeks after calculated transmission date. All other patients were treated between 12 and 26 weeks after calculated transmission date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boceprevir, Peginterferon and Ribavirin | SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks. | 5 participants |
Secondary
SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1.
The number of patients who were undetectable for HCV at week one that had an undetectable HCV RNA load 12 weeks after the end of treatment
Time frame: 12 weeks
Population: All patients having a rapid viral response at week 4 had a sustained viral response at 12(SVR12) weeks after treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boceprevir, Peginterferon and Ribavirin | SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1. | 5 participants |
Secondary
SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4).
The outcome is a number of all patients who started treatment having an undetectable HCV RNA 12 weeks after the end of therapy
Time frame: 12 weeks
Population: Total intention to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Boceprevir, Peginterferon and Ribavirin | SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4). | 49 participants |