Dutch Acute HCV in HIV Study (DAHHS) (DAHHS)

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.

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Boceprevir

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • AMC
  • Amsterdam, Netherlands
    • OLVG
  • Amsterdam, Netherlands
    • Slotervaart
  • Arnhem, Netherlands
    • Ziekenhuis Rijnstate
  • Groningen, Netherlands
    • UMCG
  • Maastricht, Netherlands
    • MUMC
  • Nijmegen, Netherlands
    • Radboud Umcn
  • Utrecht, Netherlands
    • UMCU
  • Zuid Holland
    • Rotterdam, Zuid Holland, Netherlands, 3000CA
      • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Boceprevir, peginterferon ribavirin; All patients were intended to be treated in the 12 week peginterferon, ribavirin and boceprevir arm.	Drug: Boceprevir; Other Names: Victrelis

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Radboud University Medical Center; University Medical Center Groningen; Maastricht University Medical Center; UMC Utrecht; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Rijnstate Hospital; Onze Lieve Vrouwe Gasthuis; Slotervaart Hospital
• Investigators: Principal Investigator: Bart Rijnders, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Popping S, Cuypers L, Claassen MAA, van den Berk GE, De Weggheleire A, Arends JE, Boerekamps A, Molenkamp R, Koopmans MPG, Verbon A, Boucher CAB, Rijnders B, van de Vijver DAMC. Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals. Viruses. 2022 Sep 2;14(9):1953. doi: 10.3390/v14091953.
• Hullegie SJ, Claassen MA, van den Berk GE, van der Meer JT, Posthouwer D, Lauw FN, Leyten EM, Koopmans PP, Richter C, van Eeden A, Bierman WF, Newsum AM, Arends JE, Rijnders BJ. Boceprevir, peginterferon and ribavirin for acute hepatitis C in HIV infected patients. J Hepatol. 2016 Apr;64(4):807-12. doi: 10.1016/j.jhep.2015.12.004. Epub 2015 Dec 12.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Estimate): April 1, 2016
• Last Update Submitted That Met QC Criteria: March 2, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Slow Virus Diseases; Hepatitis; HIV Infections; Hepatitis C; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: NL44825.078.13