BS-02 is a randomised, double-blind, placebo-controlled, phase 1 dose escalation study to assess the safety, tolerability and immunogenicity of FluBHPVE6E7, in women infected with HPV-16. with cervical cytological evaluation negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low grade squamous intraepithelial lesion (LSIL), or low-grade cervical intraepithelial neoplasia (CIN1).
FluBHPVE6E7 is an influenza virus vector that was modified on several levels to be used as an immunotherapeutic agent against human papillomavirus (HPV) infections, and precancers and cancers induced by HPV. Study BS-02 investigates the safety, tolerability and immunogenicity of FluBHPVE6E7 in HPV-16 infected women. FluBHPVE6E7 is administered three times at two dose levels. The first dose is administered into the cervix, subsequent doses are administered intramuscularly.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
20
Intracervical administration for first dose followed by intramuscular administration for subsequent doses at recommended dose level and determined schedule
Intracervical administration for first dose followed by intramuscular administration for subsequent doses at determined schedule
Univerzitná nemocnica Bratislava
Bratislava, Slovakia
RECRUITINGFrequency and severity of adverse events (AEs)
The severity of the adverse event is assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Time frame: 7 days
Induction of HPV-specific T-cell response following FluBHPVE6E7 administration
To evaluate the induction of HPV16 E6- and E7-specific T-cells (%) by IFN-gamma ELISPOT analysis.
Time frame: 16 weeks
Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration
To evaluate the induction of systemic vector-specific antibodies by HAI assay.
Time frame: 16 weeks
Local HPV clearance
To evaluate the status of HPV-16 infection by HPV test (yes or no).
Time frame: 16 weeks
Cervical cytology
To evaluate changes in cervical cytology by Pap smear. Results are reported as Pap results according to the Bethesda System.
Time frame: 16 weeks
Biodistribution: Detection of FluBHPVE6E7 in blood samples
To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in blood samples by RT-qPCR (copies per ml blood).
Time frame: 16 weeks
Biodistribution: Detection of FluBHPVE6E7 in saliva
To evaluate the presence of FluBHPVE6E7 by qualitative real-time PCR assay specific for influenza B virus (positive or negative).
Time frame: 16 weeks
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Viral shedding: Detection of FluBHPVE6E7 in vaginal secretion samples
To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in vaginal secretion samples by RT-qPCR (copies per sample).
Time frame: 16 weeks
Number of participants with adverse events (type, frequency, severity).
To assess the safety and tolerability of FluBHPVE6E7 by monitoring the type, frequency, and severity of AEs.
Time frame: 16 weeks