Study of FluBHPVE6E7 in HPV-16 Infected Women

BlueSky Immunotherapies

Status and phase

Completed

Phase 1

Conditions

HPV Infection

Treatments

Biological: FluBHPVE6E7

Study type

Interventional

Funder types

Industry

Identifiers

NCT04490512

BS-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment

28 patients

Sex

Female

Ages

18 to 49 years old

Volunteers

No Healthy Volunteers

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 histologically confirmed cervical intraepithelial neoplasia 1 (CIN1) or 2 (CIN2) for whom a "wait-and-see" approach for the study period is indicated
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
Current cervical intraepithelial neoplasia 3 (CIN3)
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