Efficacy of Remdesivir in Hospitalized Adult Patients with Tick-Borne Encephalitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the efficacy of remdesivir in reducing neuronal injury during tick-borne encephalitis infection, as quantified by serum neurofilament light chain (S-NfL) levels. 5

Secondary objectives include the assessment of:

• Disease severity, cognitive function, fatigue, and pain severity following infection.
• Safety via the monitoring of serious adverse events (SAEs) potentially related to the investigational medicinal product.
• Additional biomarkers of injury, including neurofilament levels in cerebrospinal fluid (CSF) and glial fibrillary acidic protein (GFAP) levels to assess glia cell injury.
• The impact of clinical and biological variables on treatment outcomes, such as treatment duration, initiation timing, CNS inflammation, flavivirus vaccination status, co-infections, demographics, comorbidities, concomitant medication, anti-TBE antibody levels, autoantibodies against type I interferons, and TBEV RNA detection.
• The influence of pharmacokinetics, specifically remdesivir and GS-441524 concentrations, as well as host genomic factors and proteomic profiles on clinical outcomes.

The sponsor did not provide information regarding the total number of participants. The study population consists of adult patients, aged 18 years or older, including both males and females. Participants are selected based on a clinically suspected infection of tick-borne encephalitis according to ECDC definitions. Inclusion requires hospitalization within seven days prior to the initiation of the study treatment and laboratory confirmation via positive anti-TBEV IgM in blood or cerebrospinal fluid, or detectable TBEV RNA in a clinical specimen. The study aims to evaluate the effect of remdesivir on neuronal injury as measured by serum neurofilament light chain levels.

This phase 2, multicenter, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy of remdesivir in adult patients hospitalized for tick-borne encephalitis. Participants are assigned to receive either remdesivir via intravenous infusion or a mannitol placebo. The primary objective is to assess the effect of the investigational product on neuronal injury, specifically measuring serum neurofilament light chain levels at week 4 following the initiation of treatment. The study involves a screening process to confirm eligibility based on clinical suspicion of infection, positive anti-TBEV IgM, or detectable TBEV RNA. Following treatment initiation, subsequent follow-up visits occur at week 4, week 12, week 26, and week 52 to monitor neurocognitive function, fatigue severity, and health-related quality of life. The total duration of participant involvement extends up to 52 weeks from the start of treatment. Secondary endpoints include the assessment of GFAP levels, mortality, and hospital-free days. The trial is expected to be completed by the end of 2028.

The experimental medication consists of remdesivir in a pharmaceutical form designated as PHF00230MIG. This substance is administered via intravenous infusion at a dosage of 200 mg.

The control group receives a placebo consisting of electrolytes. The active substance in this comparator is mannitol, provided in the pharmaceutical form PHF00230MIG at a volume of 1000 ml via intravenous infusion.

The primary efficacy endpoint is the level of serum neurofilament light chain (S-NfL) at week 4 following the initiation of treatment, which is analyzed comparatively between the remdesivir and placebo arms to evaluate neuronal injury during tick-borne encephalitis infection.

Secondary efficacy assessments include:

• Cognitive testing targeting memory, learning, working memory, processing speed, attention, and executive functions, measured at week 12, week 26, and week 52 using a CE-marked digital neurocognitive test battery to determine a composite cognitive score and individual test scores.
• Cognitive screening using the MoCA during the early phase at week 4.
• Fatigue Severity Scale assessments conducted at week 4, 12, 26, and 52.
• Visual Analogue Scale (VAS) scores recorded on day 1, day 5, and the last day of treatment if applicable.
• Neurological status evaluation at week 12 compared to the start of treatment.
• Self-reported health-related quality of life via the SF-36 questionnaire at week 4, 12, 26, and 52.
• GFAP levels in blood and/or cerebrospinal fluid (CSF) measured at day 1, day 5, week 4, week 12, and week 52.
• CSF neurofilament concentrations measured at day 1, day 5, week 4, and week 12.
• S-NfL levels at day 1, day 5, week 4, week 12, and week 52.
• Mortality at the end of the trial.
• Hospital-free days alive during study participation.
• Days on advanced respiratory support from the start to the end of the trial.
• TBEV RNA detection and quantification in CSF, blood, and saliva.
• Anti-TBE antibody concentrations and neutralizing antibody levels in CSF, blood, or saliva.
• Anti-type I interferon autoantibodies in CSF and/or blood.
• Remdesivir and GS-441524 concentrations in CSF, blood, and/or urine on day 5.