Phase 1 Dose-escalation Study of FluBHPVE6E7 in HPV16-infected Women

Randomised, Double-blind, Placebo-controlled Phase 1 Dose-escalation Study of FluBHPVE6E7 in HPV16-infected Women with NILM, ASC-US, LSIL or Low-grade CIN

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).

Study Overview

• Status: Recruiting
• Conditions: HPV Infection; HPV-Related Cervical Carcinoma
• Intervention / Treatment: Biological: FluBHPVE6E7; Drug: Placebo

Detailed Description

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
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BlueSky Clinical Operations; Phone Number: +43 664 1888028; Email: clinical@bluesky-itx.com

Study Locations

• Slovakia
  • Bratislava, Slovakia, 82606
    • Recruiting
    • Univerzitna nemocnica Bratislava
    • Contact: Phone Number: 111 00421 2 48234

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females, 18-49 years of age with HPV16 infection and 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)
• HPV16 infection has been confirmed at least twice by a validated HPV test separated by at least 3 months
• Satisfactory colposcopy
• No clinically significant out of range haematological, renal or hepatic laboratory tests
• Normal screening ECG or screening ECG with no clinically significant findings, as judged by the investigator
• Negative serum pregnancy test at screening
• Agree to use a reliable form of contraception during the whole study period.
• Provides written informed consent

Exclusion Criteria:

• Any vaccination within 6 weeks of day 0
• Active significant viral infections including influenza, CMV, and EBV within 30 days of receiving study treatment
• Co-infection with hepatitis B, hepatitis C, or HIV or having other immune deficient states
• Current Bacterial Vaginosis (BV) infection
• Current high-grade cervical intraepithelial neoplasia (CIN2/3)
• Prior history of or current malignancy, vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), atypical glandular cells (AGC), adenocarcinoma in situ (AIS) or any suspicion of either micro-invasive or invasive disease
• Pregnancy, breastfeeding
• Influenza-like illness (ILI) within 3 months of day 0
• Known hypersensitivity to oseltamivir or any of its components
• Any anatomical condition of the cervix, including that resulting from previous cervical surgery, congenital malformation or other condition, that would interfere with a complete evaluation of the cervix
• Current pelvic inflammatory disease, cervicitis, or other gynaecological infection as per colposcopy and clinical examination
• Serious, concomitant disorder, including active systemic infection requiring treatment
• Presence of acute or chronic bleeding or clotting disorder, or use of blood thinners within 2 weeks of day 0
• A proven or suspected autoimmune disease
• Immunosuppression including any concurrent condition requiring the continued use of systemic or topical steroids, or the use of immunosuppressive agents, disease modifying doses of anti-rheumatic drugs, and biologic disease modifying drugs. Any immunosuppressive agents containing corticosteroids or monoclonal antibodies specific for the treatment of obstructive airway, ear or vestibular diseases are permissible.
• Acute or history of Herpes genitalis
• Prior major surgery within 4 weeks of day 0
• Administration of any blood product within 3 months of enrolment
• Any current significant cardiac, hepatic or renal disease or history of clinically significant, medically unstable disease
• Any current or history of neurological disease including history of seizures
• Participation in another experimental protocol/use of investigational drug during the prior two months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FluBHPVE6E7; intracervical and intramuscular 0.5 ml per dose 3 doses (12 weeks)	Biological: FluBHPVE6E7; Intracervical administration for first dose followed by intramuscular administration for subsequent doses at recommended dose level and determined schedule
Placebo Comparator: Placebo; intracervical and intramuscular 0.5 ml per dose 3 doses (12 weeks)	Drug: Placebo; Intracervical administration for first dose followed by intramuscular administration for subsequent doses at determined schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency 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.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	16 weeks
Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration	To evaluate the induction of systemic vector-specific antibodies by HAI assay.	16 weeks
Local HPV clearance	To evaluate the status of HPV-16 infection by HPV test (yes or no).	16 weeks
Cervical cytology	To evaluate changes in cervical cytology by Pap smear. Results are reported as Pap results according to the Bethesda System.	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).	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).	16 weeks
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).	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.	16 weeks

Collaborators and Investigators

• Sponsor: BlueSky Immunotherapies GmbH

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: BS-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No