Clinical trial NCT01912495: Dutch Acute HCV in HIV Study (DAHHS)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Human Immunodeficiency Virus
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Onze Lieve Vrouwe Gasthuis
name: UMC Utrecht
name: University Medical Center Groningen
name: Maastricht University Medical Center
name: Rijnstate Hospital
name: Slotervaart Hospital
name: Radboud University Medical Center
First posted: 2013-07-31
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 12 weeks
Secondary outcomes:
measure: SVR 12 Weeks After the End of All Therapy in the Entire Study Population (With or Without RVR4).
timeFrame: 12 weeks
measure: SVR 12 Weeks After End of Therapy in Patients With Already a RVR at Week 1.
timeFrame: 12 weeks
measure: SVR 12 Weeks After End of Therapy in Patients That Started Therapy ≤12weeks After the Presumed HCV Infection Date Versus Those After 12 Weeks.
timeFrame: 12 weeks
measure: Alterations of Biomarkers by Therapy Induced Viral Eradication: Viral Sequencing, Mutation Analysis, Gene Expression Analysis, and RNA Analysis.
timeFrame: 72 weeks
measure: Safety: Treatment Related (Serious) Adverse Events ((S)AE) and Treatment Discontinuation for (S)AE.
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid Holland
city: Amsterdam
country: Netherlands
facility: AMC
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: Slotervaart
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Groningen
country: Netherlands
facility: UMCG
city: Maastricht
country: Netherlands
facility: MUMC
city: Nijmegen
country: Netherlands
facility: Radboud UMCN
city: Utrecht
country: Netherlands
facility: UMCU
Study officials:
affiliation: Erasmus Medical Center
name: Bart Rijnders, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.