Prime-boost Vaccine Study in Women With Low-grade Cervical HPV 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
• Sexual abstinence, only if the participant refrains from heterosexual intercourse during the entire study period and it is the usual lifestyle of the participant
• 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, e.g. severe allergy to eggs.
• 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.
• Receipt of any adenoviral based vaccine within 3 months prior to administration of ChAdOx1 HPV on Day 0, or plan to receive an adenoviral-based vaccine within 3 months after Day 0.
• 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)
• Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.