BS-01 is a randomised, double-blind, placebo-controlled, phase 1 dose escalation study assessing safety, tolerability and immunogenicity of FluBHPVE6E7, changes in the HPV infection status and cervical cytology, and biodistribution in HPV-16 infected women with normal cytology, CIN1 or CIN2. The safety and immunogenicity of two dose levels, 7.5 log10 and 9.0 log10 fTCID50/dose of FluBHPVE6E7 are assessed after three subcutaneous administrations. In addition the safety of 9.0 log10 fTCID50/dose of FluBHPVE6E7 is assessed after three intradermal or intramuscular administrations.
BS-01 is a randomised, placebo-controlled, double- blind phase 1 dose-escalation study in women with normal cytology, CIN1 or CIN2. The primary objective is to assess the safety and tolerability of FluBHPVE6E7. Secondary objectives are the assessment of the systemic immune responses to immunisations with FluBHPVE6E7, changes in HPV infection status and cervical cytology, and biodistribution. Study medication is administered three times (Day 0, Week 4, Week 12). Study participants are randomised at a ratio of 3:1 for FluBHPVE6E7 or placebo. The first cohort is treated subcutaneously at dose level 7.5 log10 fTCID50/dose. The second cohort is treated subcutaneously at 9.0 log10 fTCID50/dose. Interim safety reviews are performed by a Data Monitoring Committee. After completion of the dose-escalation and in order to collect additional safety data on the highest safe and tolerated dose level, additional study participants are enrolled into expansion cohorts treated three times subcutaneously, intradermally or intramuscularly at 9.0 log10 fTCID50/dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
28
Multiple subcutaneous, intradermal or intramuscular administrations
Medical University of Vienna
Vienna, Austria
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: 7 days
Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration
To evaluate of the induction of systemic vector-specific antibodies by HAI assay
Time frame: 16 weeks
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
Induction of HPV-specific CD4+ and CD8+ T-cells following FluBHPVE6E7 administration
To evaluate the induction of HPV16 E6- and E7 specific T-cells (%) by ICS and FACS analysis
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
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Biodistribution: Detection of FluBHPVE6E7 in nasal secretions
To evaluate the presence of FluBHPVE6E7 by qualitative real-time PCR assay specific for influenza B virus (positive or negative)
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