Dutch Acute HCV in HIV Study (DAHHS)

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of 12 Week Boceprevir in Addition to Standard of Care Therapy Consisting of Peginterferon-alpha-2b and Ribavirin for the Treatment of Acute HCV Genotype 1 in HIV Co-infected Patients. A Proof of Concept Feasibility Clinical Trial.

Conditions
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Hepatitis C, Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: Boceprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented recent HCV genotype 1 infection (≤26 weeks old at the time of the baseline visit) according to definition mentioned below. 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. A previously performed HCV RNA plasma measurement can be used for screening if <4 weeks old. On HAART at the time of screening. Minimum age 18 years. Exclusion Criteria: 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. 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). 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. HAART was started <4 weeks before baseline visit. 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. Patient that virologically failed HAART in the past

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boceprevir, peginterferon ribavirin<br>All patients were intended to be treated in the 12 week peginterferon, ribavirin and boceprevir arm. | Drug: Boceprevir<br> <br> * Other names: Victrelis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 weeks | 
| 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 | 12 weeks | 
| 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. | 12 weeks | 
| 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. | only serious adverse events are recorded in this secondary endpoint | 72 weeks |