Study of FluBHPVE6E7 in HPV-16 Infected Women

Overview

BS-01 is a phase 1, randomised, double-blind, placebo- controlled dose escalation trial designed to assess the safety, tolerability, immunogenicity, changes in HPV infection status and cervical cytology, and biodistribution in HPV16 positive women with normal cytology or low-grade cervical intraepithelial neoplasia after three subcutaneous administrations. The safety and immunogenicity of two dose levels, 7.5 log10 and 9.0 log10 fTCID50/dose of FluBHPVE6E7 are assessed.

Full Title of Study: “Randomised, Double-blind, Placebo-controlled Phase 1 Dose-escalation Study of FluBHPVE6E7 in HPV-16 Infected Women With Normal Cytology or Low-grade Cervical Intraepithelial Neoplasia”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 31, 2021

Detailed Description

BS-01 is a randomised, placebo-controlled, double- blind phase 1 dose-escalation study in women with normal cytology or low-grade cervical intraepithelial neoplasia. The primary objective is to assess the safety and tolerability of subcutaneous administrations 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 subcutaneously 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 at dose level 107.5 fTCID50/dose. The second cohort is treated at 109 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, four additional study participants are enrolled into an expansion cohort.

Interventions

  • Biological: FluBHPVE6E7
    • Multiple subcutaneous administrations

Arms, Groups and Cohorts

  • Experimental: FluBHPVE6E7
    • Multiple administration of FluBHPVE6E7
  • Placebo Comparator: Placebo
    • Multiple administration of buffer solution

Clinical Trial Outcome Measures

Primary Measures

  • Number of participants with adverse events (type, frequency, severity).
    • Time Frame: 7 days
    • To assess the safety and tolerability of FluBHPVE6E7 by monitoring the type, frequency, and severity of AEs

Secondary Measures

  • Hemagglutination Inhibition (HAI) Geometric Mean Titers (GMTs) following FluBHPVE6E7 administration
    • Time Frame: 16 weeks
    • To evaluate of the induction of systemic vector-specific antibodies by HAI assay
  • Induction of HPV-specific T-cell response following FluBHPVE6E7 administration
    • Time Frame: 16 weeks
    • To evaluate the induction of HPV16 E6- and E7-specific T-cells (%) by IFN-gamma ELISPOT analysis
  • Induction of HPV-specific CD4+ and CD8+ T-cells following FluBHPVE6E7 administration
    • Time Frame: 16 weeks
    • To evaluate the induction of HPV16 E6- and E7 specific T-cells (%) by ICS and FACS analysis
  • Local HPV clearance
    • Time Frame: 16 weeks
    • To evaluate the status of HPV-16 infection by HPV test (yes or no)
  • Cervical cytology
    • Time Frame: 16 weeks
    • To evaluate changes in cervical cytology by Pap smear. Results are reported as Pap results according to the Bethesda System
  • Biodistribution: Detection of FluBHPVE6E7 in blood samples
    • Time Frame: 16 weeks
    • To evaluate the presence of FluBHPVE6E7 by quantification of FluBHPVE6E7 genome copies in blood samples by RT-qPCR (copies per ml blood)
  • Biodistribution: Detection of FluBHPVE6E7 in nasal secretions
    • Time Frame: 16 weeks
    • To evaluate the presence of FluBHPVE6E7 by qualitative real-time PCR assay specific for influenza B virus (positive or negative)
  • Number of participants with adverse events (type, frequency, severity).
    • Time Frame: 16 weeks
    • To assess the safety and tolerability of FluBHPVE6E7 by monitoring the type, frequency, and severity of AEs

Participating in This Clinical Trial

Inclusion Criteria

  • Females in general good health, EITHER 18-49 years of age with HPV-16 infection and cervical cytological evaluation with a normal result, OR 25-49 years of age, with HPV-16 infection and low-grade cervical intraepithelial neoplasia (CIN1), at screening – HPV-16 infection has been confirmed at least twice by a validated HPV test separated by at least 3 months – Satisfactory colposcopy (i.e. the entire cervix as well as the entire squamocolumnar junction can be visualized by colposcopy and there is no evidence of invasive cancer) – 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. Reliable forms of contraception are hysterectomy or bilateral tubal ligation, hormonal methods (oral, injected, implanted or transdermal), intrauterine device, barrier method plus spermicide, history of a single male partner with vasectomy, or a history of abstinence deemed credible by the investigator. Furthermore, male partners should use condoms during the whole study period. – Provides written informed consent Exclusion criteria:
  • Seropositivity (i.e. HAI titres >1:20) to the vector-derived wild type virus – Any vaccination within 6 weeks of receiving study treatment – 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 – Prior history of or current malignancy, high-grade cervical intraepithelial neoplasia (CIN2/3), 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) during the preceding 3 months – 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 (e.g. anticoagulants or antiplatelet drugs) 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 (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate), and biologic disease modifying drugs such as TNF-α inhibitors (e.g. infliximab, adalimumab or etanercept). Corticosteroids must be discontinued > 4 weeks prior to day 0 of study medication administration. Eye drops or ear drops containing corticosteroids 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 (e.g. chronic renal failure; angina, myocardial ischemia or infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias) – 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 – Any condition that, in the judgment of the investigator, might prevent safe participation in the study or interfere with study objectives – Unability to comply with the protocol requirements
  • Gender Eligibility: Female

    Minimum Age: 18 Years

    Maximum Age: 49 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • BlueSky Immunotherapies GmbH
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Contact(s)
      • Thomas Muster, PhD, +4369910941071, clinical@bluesky-itx.com

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