Tick-Borne Encephalitis (TBE) Remdesivir Efficacy Assessment Trial (TREAT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Stockholm – SLSO

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2026-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Stockholms läns sjukvårdsområde, Region Stockholm

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to evaluate the effect of remdesivir on neuronal injury during TBE virus infection, as measured by serum neurofilament light chain (S-NfL) levels.

Secondary objectives 21

1. To evaluate the effect of remdesivir treatment on post-TBE cognitive function.
2. To evaluate the effect of remdesivir treatment on post-TBE fatigue.
3. To evaluate the effect of remdesivir on pain severity.
4. To evaluate the safety of remdesivir in terms of reported SAEs possibly related to IMP.
5. To evaluate the effect of remdesivir on disease severity.
6. To evaluate whether earlier initiation of remdesivir influences clinical outcomes.
7. To evaluate whether treatment duration affects clinical outcomes.
8. To evaluate whether severity or duration of CNS inflammation at admission affects treatment outcome.
9. To assess whether flavivirus (TBE, Yellow Fever, or Japanese Encephalitis vaccination status influences treatment outcome.
10. To evaluate whether demographic and Day 1 clinical characteristics (sex, BMI, comorbidities, age) influence treatment outcome.
11. To evaluate whether concomitant medication influences treatment outcome.
12. To evaluate whether tick-borne co-infections influence treatment outcome.
13. To evaluate the effect of remdesivir on neuronal injury during TBE infection by measuring S-NfL at additional time points beyond those specified in the primary objective.
14. To evaluate neuronal injury using neurofilament (NfL) levels in CSF.
15. To evaluate glia cell injury using glial fibrillary acidic protein (GFAP) levels.
16. To evaluate whether remdesivir (GS-5734) and/or GS-441524 concentrations affect treatment outcome.
17. To evaluate whether quantitative and qualitative anti-TBE antibody levels affect treatment outcome.
18. To evaluate whether autoantibodies against type I interferons affect treatment outcome.
19. To evaluate whether detection or the level of TBEV RNA affects treatment outcome.
20. To evaluate whether host genomic factors affect treatment outcome.
21. To evaluate whether host proteomic profiles affect treatment outcome.

Conditions and MedDRA coding

Tick-Borne Encephalitis (TBE)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Need of hospitalization at screening
2. 2. Clinically suspected TBE according to ECDC definition
3. 3. Hospitalization ≤ 7 days prior to start of study treatment. The 7-day period is counted as 7 full calendar days prior to the day of IMP initiation, regardless of time of hospitalization or treatment start. E.g., admission Apr 10 at 08:00 allows IMP initiation up until Apr 17 23:59.
4. 4. Positive anti-TBEV IgM in blood or CSF, or detectable TBEV RNA in a clinical specimen (blood, CSF or urine) according to local test results
5. 5. ≥18 years old
6. 6. The patient has given their written consent to participate in the trial

Exclusion criteria 8

1. 1. Hypersensitivity to the active substances or ingredients of remdesivir or against any residues according to SmPC.
2. 2. Non-Swedish speaking
3. 3. Other contraindication to remdesivir treatment
4. 4. Chronic kidney disease stadium 4 and 5
5. 5. Pregnancy (verified by urine pregnancy test at screening)
6. 6. Unable to comply with protocol requirements
7. 7. Before TBE-diagnosis, diagnosed with dementia or other chronic cognitive dysfunction.
8. 8. Treatment or disease which, according to the investigator, can affect treatment or trial results.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. S-NfL level at Week 4 after initiation of treatment, analyzed comparatively between the remdesivir and placebo arms.

Secondary endpoints 21

1. Comprehensive cognitive testing targeting memory and learning, working memory, processing speed, attention and executive functions, operationalized as a composite cognitive score and also analyzed as individual test scores. Measured at week 12, 26 and 52, after treatment start, using a CE-marked digital neurocognitive test battery, analyzed comparatively between treatment arms. Cognitive screening (MoCA) performed in early phase (week 4).
2. Fatigue Severity Scale measured at week 4, 12, 26 and 52, after treatment start, analyzed comparatively between treatment arms.
3. Visual Analogue Scale (VAS) scores at Day 1, 5 and, if longer duration of treatment, also on the last day of treatment. Analyzed comparatively between treatment arms.
4. Detailed methods to record AEs and SAEs are described in section 9.3. The definition of SAEs is included in this study protocol in section 9.1.
5. • Number of hospital-free days alive during study participation. • Mortality at End of Trial • Days on advanced respiratory support from Start to End of Trial • Neurological status (46) at Week 12 compared to at start of treatment. • Patient questionnaire (SF-36) assessing self-reported health-related quality of life, at week 4, 12, 26 and 52. Analyzed comparatively between treatment arms.
6. Time from hospitalization to start of treatment in relation to NfL/GFAP and/or the composite cognitive score at Week 4 in the remdesivir arm.
7. Number of days of remdesivir treatment (5, 6, 7, 8, 9 or 10 days) in relation to NfL/GFAP and/or the composite cognitive score at Week 4 in the remdesivir arm.
8. Time from anamnestic fever onset to treatment initiation in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
9. Number and timing of previous TBE-, Yellow Fever -or Japanese Encephalitis vaccinations in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
10. Sex, anamnestic height and weight (BMI), comorbidities, age in relation to NfL/GFAP the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
11. Concomitant medication use in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
12. Tick-borne co-infections confirmed by blood analysis in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
13. S-NfL levels at time points other than Week 4 (i.e., Day 1, Day 5, Week 4, Week 12, and Week 52), analyzed comparatively between treatment arms.
14. CSF neurofilament concentrations before and after treatment initiation (i.e., Day 1, Day 5, Week 4 and Week 12), analyzed comparatively between treatment arms.
15. GFAP levels in blood and/or CSF before and after treatment initiation (i.e., Day 1, Day 5, Week 4, Week 12, and Week 52), analyzed comparatively between treatment arms.
16. Concentrations of remdesivir and GS-441524 in CSF, blood, and/or urine on Day 5 in relation to NfL/GFAP and/or the composite cognitive score at Week 4 in the remdesivir arm.
17. Anti-TBE (IgG, IgM, and/or IgA) and neutralizing antibody concentrations in CSF, blood and/or saliva (before and/or after treatment initiation) in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms
18. Concentrations of anti–type I interferon autoantibodies in CSF and/or blood in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
19. Detection and/or quantification of TBEV RNA in CSF, blood, and saliva (before and/or after treatment initiation) in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
20. Host genomic variants in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.
21. Host proteomic signatures in relation to NfL/GFAP and/or the composite cognitive score at Week 4, analyzed comparatively between treatment arms.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Stockholm – SLSO

Sponsor organisation

Region Stockholm – SLSO

Address

Solnavagen 1 E, S:t Matteus S:t Matteus

City

Stockholm

Postcode

113 65

Country

Sweden

Scientific contact point

Organisation

Region Stockholm – SLSO

Contact name

Helena Hervius Askling

Public contact point

Organisation

Region Stockholm – SLSO

Contact name

Helena Hervius Askling

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications