The TARGET-EBV in MS Study: Targeting Epstein–Barr Virus with Tenofovir Alafenamide in Multiple Sclerosis
The TARGET-EBV in MS study aims to investigate whether antiviral treatment targeting EBV can reduce neuronal damage and disease activity in MS.
Disease: Multiple sclerosis
Type of study: Interventional trial
Coordinating Investigator: Marton Kønig
Study Director/Overall Project Coordinator for EBV-MS (Horizon Europe): Øivind Torkildsen.
Study Director OUH: Gro Owren Nygaard
Background: Epstein-Barr virus (EBV) infection is the strongest known environmental risk factor for multiple sclerosis (MS), but it remains unclear whether EBV only triggers the disease or also contributes to ongoing disease activity. Current disease-modifying therapies mainly target downstream inflammatory pathways and do not directly address a potential viral driver of MS.
Tenofovir alafenamide fumarate (TAF) is a well-established antiviral drug used in the treatment of hepatitis B and in HIV prevention. Experimental studies have shown that TAF inhibits lytic replication of EBV, and epidemiological observations suggest that antiretroviral therapies may reduce MS disease activity. The TARGET-EBV in MS study aims to investigate whether antiviral treatment targeting EBV can reduce neuronal damage and disease activity in MS.
The primary objective is to evaluate whether TAF reduces neuronal damage in MS patients treated with anti-CD20 therapy.
The primary endpoint is the change in cerebrospinal fluid neurofilament light chain (NfL) levels from baseline to week 52. Key secondary outcomes include changes in microglial activation measured by TSPOPET imaging, fatigue assessed by patient-reported outcomes, paramagnetic rim lesions on MRI, and EBV viral shedding and viral load.
Design: This is a prospective, multicentre, randomised, double-blind, placebo-controlled phase IIb clinical trial, as a part of the EBV-MS Horizon Europe project. Participants receiving stable anti-CD20 therapy will be randomised 1:1 to receive either TAF (100 mg daily) or placebo for 12 months. Approximately 600 patients will be screened to identify eligible participants, and 60 patients will be included in the trial. The study includes advanced biomarker assessments such as cerebrospinal fluid sampling, quantitative susceptibility MRI, and TSPOPET imaging.
Status: The first version of the protocol is approved, but dosing is under revision. Thus, the study is currently in the preparatory phase. The first patient is expected to be enrolled in August 2026. Recruitment is anticipated to last approximately one year, and participants will be followed for 12 months, with study completion expected in 2028.
Participating centres
Norway
- Oslo University Hospital, Oslo
- Haukeland University Hospital, Bergen
- Vestre Viken Hospital, Drammen
- Akershus University Hospital, Lørenskog
- Stavanger University Hospital, Stavanger
Finland
- Turku PET Centre, Turku
Funding
- Horizon Europe
- The Research Council of Norway, Neuro-SysMed
- Oslo University Hospital
- Haukeland University Hospital
- The University of Bergen
- Participating hospitals
- Gilead Sciences, USA