Clinical trial NCT05829629: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HPV Infection
HPV-Related Cervical Carcinoma
Lead sponsor: BlueSky Immunotherapies GmbH
Sponsor class: INDUSTRY
First posted: 2023-04-26
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Frequency and severity of adverse events (AEs)
timeFrame: 7 days
Secondary outcomes:
measure: Induction of HPV-specific T-cell response following FluBHPVE6E7 administration
timeFrame: 16 weeks
measure: Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration
timeFrame: 16 weeks
measure: Local HPV clearance
timeFrame: 16 weeks
measure: Cervical cytology
timeFrame: 16 weeks
measure: Biodistribution: Detection of FluBHPVE6E7 in blood samples
timeFrame: 16 weeks
measure: Biodistribution: Detection of FluBHPVE6E7 in saliva
timeFrame: 16 weeks
measure: Viral shedding: Detection of FluBHPVE6E7 in vaginal secretion samples
timeFrame: 16 weeks
measure: Number of participants with adverse events (type, frequency, severity).
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: Univerzitná nemocnica Bratislava
Study officials:
References: