Prime-boost Vaccine Study in Women With Low-grade Cervical HPV Lesions
Prime-boost Vaccine Study in Women With Low-grade Cervical HPV Lesions
A Phase 1b/2 multi-centre study evaluating the safety, efficacy and immunogenicity of
 prime-boost vaccines ChAdOx1-HPV and MVA-HPV in women with HPV related low grade cervical
 lesions.
The study consists of an open label, non-randomised, dose escalation Lead in phase. 9
 participants with high-risk HPV, in cohorts of 3 in 3 dose ascending groups, will be
 vaccinated after SMC safety data reviews.

 This is followed by a blinded, randomised Main phase with 96 participants with high-risk HPV,
 in parallel running dose cohorts (three different doses of ChAdOx1-HPV plus two different
 doses of MVA-HPV versus placebo plus placebo boost). At least 60 of these participants will
 take part in the immunogenicity sub-study.

 A blinded, randomised expansion phase investigating the effects of up to two different main
 phase doses against placebo will be further defined prior to commencing this phase of the
 study.
Inclusion Criteria:

 -  Females aged ≥25 and ≤55 years of age at screening.

 -  Persistent hrHPV infection defined as a documented cervical infection with hrHPV
 type(s) in the 6 to 18 months prior to screening and confirmed at screening
 (participants in the main and expansion phases only). Participants in the lead-in
 phase are only required to have the screening result.

 -  Low-grade cervical lesion (CIN1 or HPV-related change only) confirmed by histology
 and/or cytology report within the 1 year prior to screening.

 -  Not pregnant or breast feeding and one of the following:

 -  Of non-childbearing potential (i.e. women who have had a hysterectomy or tubal
 ligation or are postmenopausal, as defined by no menses for at least 12 months
 and without an alternative medical cause)

 -  Of childbearing potential but agrees to practice highly effective contraception
 for 4 weeks prior to administration of the first dose of study vaccine and
 throughout the study until 8 weeks after administration of the second dose.
 Highly effective methods of contraception include one or more of the following:

 -  Male partner who is sterile (medically effective vasectomy) prior to the female
 participant's entry into the study and is the sole sexual partner for the female
 participant

 -  Hormonal (oral, intravaginal, transdermal, implantable or injectable).
 Progestogen-only hormonal contraceptives without inhibition of ovulation are not
 considered to be highly effective.

 -  An intrauterine hormone-releasing system

 -  An intrauterine device

 -  Bilateral tubal occlusion

 -  Willing to abstain from sexual activity for 48 hours prior to all swabbing procedures.

 Exclusion Criteria:

 -  Presence of any significant acute or chronic, uncontrolled medical (or psychiatric)
 illness, including blood dyscrasias.

 -  Immunosuppression as a result of underlying illness or treatment including:

 -  Use of high dose corticosteroids ( >10 mg/day prednisone or equivalent) for ≥7
 days (inhaled, otic and ophthalmic corticosteroids are permitted)

 -  Primary immune deficiency disease

 -  Use of synthetic or biologic disease-modifying antirheumatic drugs

 -  History of bone marrow or solid organ transplant

 -  History of any other clinically significant autoimmune or immunosuppressive
 disease

 -  Positive diagnostic tests (for human immunodeficiency virus, hepatitis B or hepatitis
 C) indicating chronic infection.

 -  Evidence of high-grade cervical lesions by colposcopy or by Papanicolaou (Pap) smear
 test in the 1 year prior to screening.

 -  Any history of anaphylaxis in reaction to vaccination or history of allergic reactions
 likely to be exacerbated by any component of the vaccine.

 -  Receipt of any investigational drug or investigational vaccine within 3 months prior
 to administration of ChAdOx1-HPV on Day 0, or prior participation in a clinical study
 of any HPV vaccine.

 -  Any history of receipt of any adenoviral or MVA-based vaccine.

 -  Receipt of any live vaccines within the 30 days or inactivated vaccine within the 14
 days prior to administration of ChAdOx1-HPV on Day 0 or planned to occur in the 2
 months after the Day 0 vaccination.

 -  Current or history of illicit drug use within the 6 months prior to screening.

 -  Current or history of severe alcohol abuse within the 6 months prior to screening.

 -  Any laboratory test which is abnormal and deemed by the Investigator to be clinically
 significant which will potentially affect the participation in the study.

 -  Current known infection with severe acute respiratory syndrome coronavirus 2
 (SARS-CoV-2) as evidenced by PCR laboratory testing.

 -  Any other finding that, in the opinion of the Investigator, deems the participant
 unsuitable for the study.