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

Official title

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

Overview

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).

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.

Interventions

• Biological FluBHPVE6E7
  Intracervical administration for first dose followed by intramuscular administration for subsequent doses at recommended dose level and determined schedule
• Drug Placebo
  Intracervical administration for first dose followed by intramuscular administration for subsequent doses at determined schedule

Primary outcome measures

• Frequency and severity of adverse events (AEs) [Time frame: 7 days]

Secondary outcome measures (8)

• Induction of HPV-specific T-cell response following FluBHPVE6E7 administration [Time frame: 16 weeks]
• Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration [Time frame: 16 weeks]
• Local HPV clearance [Time frame: 16 weeks]
• Cervical cytology [Time frame: 16 weeks]
• Biodistribution: Detection of FluBHPVE6E7 in blood samples [Time frame: 16 weeks]
• Biodistribution: Detection of FluBHPVE6E7 in saliva [Time frame: 16 weeks]
• Viral shedding: Detection of FluBHPVE6E7 in vaginal secretion samples [Time frame: 16 weeks]
• Number of participants with adverse events (type, frequency, severity). [Time frame: 16 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Slovakia · 1 center

• Univerzitná nemocnica Bratislava — Bratislava

Identifiers

NCT: NCT05829629 · BS-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗