Clinical trial NCT04607850: Prime-boost Vaccine Study in Women With Low-grade Cervical HPV Lesions
Official title: A Phase 1b/2, Randomised, Placebo-controlled, Dose-ranging Study to Evaluate Safety, Tolerability and Immunogenicity of a Chimpanzee Adenovirus (ChAdOx1)-Vectored Multigenotype High Risk Human Papillomavirus (hrHPV) Vaccine and Modified Vaccinia Ankara (MVA)-Vectored Multigenotype hrHPV Vaccine in Women With Low-grade HPV-related Cervical Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HPV Infection
CIN1
Lead sponsor: Barinthus Biotherapeutics
Sponsor class: INDUSTRY
First posted: 2020-10-29
Enrollment: 108
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Females aged ≥25 and ≤55 years of age at screening.
2. 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.
3. Low- grade cervical lesion (CIN1 or HPV-related change only) confirmed by histology and/or cytology report within the 1 year prior to screening.
4. 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
5. Willing to abstain from sexual activity for 48 hours prior to all swabbing procedures

Exclusion Criteria:

1. Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness, including blood dyscrasias.
2. 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
3. Positive diagnostic tests (for human immunodeficiency virus, hepatitis B or hepatitis C) indicating chronic infection.
4. Evidence of high grade cervical lesions by colposcopy or by Papanicolaou (Pap) smear test in the 1 year prior to screening.
5. 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.
6. 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.
7. 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.
8. 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.
9. Current or history of illicit drug use within the 6 months prior to screening.
10. Current or history of severe alcohol abuse within the 6 months prior to screening.
11. Any laboratory test which is abnormal and deemed by the Investigator to be clinically significant which will potentially affect the participation in the study.
12. Current known infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2)
13. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.

Primary outcomes:
measure: Incidence of adverse events to measure safety and reactogenicity
timeFrame: 3 months for the lead-in and 12 months for the main phase
Secondary outcomes:
measure: Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development
timeFrame: 3 months for lead in phase and 12 months for main phase
measure: Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection
timeFrame: 12 months for main phase only
measure: Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)
timeFrame: 12 months for main phase only
Other outcomes:
measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
timeFrame: 3 months for lead in phase and 12 months for main phase
measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
timeFrame: 3 months for lead in phase and 12 months for main phase
measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
timeFrame: 3 months for lead in phase and 12 months for main phase
measure: Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
timeFrame: 3 months for lead in phase and 12 months for main phase
Locations:
city: Antwerp
country: Belgium
facility: UZA
city: Brussels
country: Belgium
facility: Erasme Hospital
city: Brussels
country: Belgium
facility: UZ Brussel
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Parnu
country: Estonia
facility: Parnu Hospital Womens and Childrens Clinic
city: Tallinn
country: Estonia
facility: East-Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation Surgery Clinic
city: Tartu
country: Estonia
facility: Tartu University Hospital Womens Clinic
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bristol
country: United Kingdom
facility: University Hospital Bristol NHS Trust
city: Liverpool
country: United Kingdom
facility: Liverpool Women's NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: The University of Oxford, Nuffield Department of Women's & Reproductive Health
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
Study officials:
References: