The Tick-borne Encephalitis Virus (TBEV)
Conditions
Keywords
Tick-borne encephalitis, Tick-borne encephalitis virus, Human antibody therapy, Healthy volunteers, Phase I clinical trial, Intravenous administration, Monoclonal antibody
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics of the investigational monoclonal antibody TBE025 when given intravenously to healthy adult volunteers aged 18 to 55. The study aims to determine the recommended Phase II dose of TBE025 and to assess the incidence and severity of adverse events related to its administration. There is no comparison group, as this is a single-arm, open-label study. Participants will receive a single intravenous infusion of TBE025 at one of three escalating dose levels, will be monitored for safety with regular clinical and laboratory assessments, and will provide blood samples for pharmacokinetic, anti-drug antibody, and neutralization testing.
Detailed description
The tick-borne encephalitis virus (TBEV) is an infection spread by ticks that is becoming more common in Europe, including Switzerland. Currently, there is no specific treatment-care focuses on relieving symptoms. Vaccines exist, but few people get vaccinated, and sometimes the vaccine does not offer full protection. There is therefore a real need for new ways to prevent or treat this disease. TBE025 is a fully human antibody taken from people who have recovered from TBEV. It can strongly block the virus. In lab studies with mice, TBE025 was able to protect against infection, both when given before exposure and soon after infection. It also appears to be safe, with no harmful effects on other tissues. This first-in-human study (phase 1) will evaluate intravenous administration of TBE025 in healthy adult volunteers using a standard 3+3 dose-escalation design (200 mg, 600 mg, 2000 mg). Between 3 and 18 participants will be enrolled sequentially across three cohorts. The study is designed to establish the maximum tolerated dose and recommended Phase II dose, as well as to characterize the pharmacokinetics, immunogenicity, and neutralization capacity of TBE025. Participants will be followed for safety, laboratory, and pharmacokinetic assessments over a three-month period. The study will provide the first clinical data on TBE025 in humans and will inform the design of subsequent efficacy trials in populations at risk of TBEV infection.
Interventions
DRUGHuman monoclonal antibody TBE025, intravenous infusion
TBE025 is a recombinant, fully human monoclonal antibody (mAb). It is provided in single-use vials containing 20 mg/mL of protein in 5 mL of buffered solution consisting of 10 mM Histidine, 250 mM Trehalose, 10 mM Methionine, 0.05% Polysorbate 20 and water for injection, at pH 5.5. TBE025 is a clear to opalescent, colorless to brown liquid.
Sponsors
Giuseppe Pantaleo
Rockefeller University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase I, Dose escalation 3+3, Non randomized, Open Label.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults aged 18 to \<55 years * Good general health (medical history, physical exam, normal labs) * Written informed consent provided * Ability to read and understand local language * Contraception requirements : Women of childbearing potential: negative pregnancy test, surgically sterile, postmenopausal, or using highly effective contraception for 3 months post-infusion. Men: surgically sterile or using highly effective contraception (self or partner) and abstain from sperm donation for 3 months post-infusion.
Exclusion criteria
* BMI \<19 or \>30 * Infections: HIV, active hepatitis B (HBsAg), active hepatitis C * Prior participation in investigational study within 30 days * History of hypersensitivity to monoclonal antibodies * Recent surgery or unresolved adverse events * Active autoimmune disease requiring systemic treatment * Recent use of immunosuppressive agents or immunoglobulins * Immunodeficiency diagnosis * Significant cardiovascular events within 6 months * Live/attenuated vaccines within 28 days * Major surgery within 28 days * Pregnancy or breastfeeding * Professional or private link with the research team * Any condition judged by the investigator to interfere with safety or study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of TBE025 | Up to 84 days after the infusion | Number and percentage of subjects experiencing AEs, SAEs, AEs related to investigational product at each dose level |
| Incidence and severity of adverse events (AEs) | Up to 84 days after the infusion | Number and percentage of subjects experiencing AEs related to investigational product and the severity of the AEs at each dose level |
| Incidence and severity of Dose Limiting Toxicity (DLT) | Up to 21 days after the infusion. | Number and percentage of participants experiencing DLTs at each dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of TBE025 | up to 84 days after infusion | Plasma concentration measured by ELISA for each participant at each dose level |
| Presence of anti-drug antibodies | Up to 84 days after infusion | Antibodies against TBE025 measured by ELISA for each participant at each dose group |
Countries
Switzerland
Contacts
CONTACTLaura Molinari
Outcome results
None listed