Prime-boost Vaccine Study in Women With Low-grade Cervical HPV Lesions

Phase 1

Completed

• Conditions: HPV Infection; CIN1
• Interventions: Biological: ChAdOx1-HPV; Biological: Placebo; Biological: MVA-HPV

• Registration Number: NCT04607850
• Lead Sponsor: Barinthus Biotherapeutics

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.

Study Timeline

• Study First Submitted: 2020-10-22
• Study First Submitted QC: 2020-10-22
• Study First Posted: 2020-10-29
• Study Start: 2021-03-16
• Primary Completion: 2024-01-16
• Study Completion: 2024-01-16
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-30
• Last Update Posted: 2024-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 108

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^7 pfu)
Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10 vp) and MVA-HPV (1 x 10\^8 pfu)
Group 6 Placebo Saline	Placebo	Sodium Chloride (0.9%)
Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^8 vp) and MVA-HPV (1 x 10\^8 pfu)
Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10 vp) and MVA-HPV (1 x 10\^8 pfu)
Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^8 vp) and MVA-HPV (1 x 10\^7 pfu)
Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10) vp and MVA-HPV (1 x 10\^8 pfu)
Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^8 vp) and MVA-HPV (1 x 10\^7 pfu)
Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^7 pfu)
Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^7 pfu)
Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^8 vp) and MVA-HPV (1 x 10\^8 pfu)
Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^8 pfu)
Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^8 pfu)
Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10) vp and MVA-HPV (1 x 10\^8 pfu)
Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^9 vp) and MVA-HPV (1 x 10\^7 pfu)
Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose	ChAdOx1-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10 vp) and MVA-HPV (1 x 10\^7 pfu)
Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose	MVA-HPV	Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10\^10 vp) and MVA-HPV (1 x 10\^7 pfu)

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events to measure safety and reactogenicity	3 months for the lead-in and 12 months for the main phase	Measure of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse events reported.

Secondary Outcome Measures

Name	Time	Method
Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)	12 months for main phase only	The percentage of cervical lesions cleared as determined by colposcopy
Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development	3 months for lead in phase and 12 months for main phase	Measurement of the highest multi-parameter index made of CD4+ magnitude, CD4+ avidity and CD8+ magnitude at peak timepoint
Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection	12 months for main phase only	The percentage of hrHPV infection clearance

Trial Locations

Locations (16)

UZA; 🇧🇪 Antwerp, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

UZ Brussel; 🇧🇪 Brussels, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Parnu Hospital Womens and Childrens Clinic; 🇪🇪 Parnu, Estonia

East-Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

University Hospital Bristol NHS Trust; 🇬🇧 Bristol, United Kingdom

Liverpool Women's NHS Foundation Trust; 🇬🇧 Liverpool, United Kingdom

Aberdeen Royal Infirmary; 🇬🇧 Aberdeen, United Kingdom

Royal Victoria Infirmary; 🇬🇧 Newcastle Upon Tyne, United Kingdom

The University of Oxford, Nuffield Department of Women's & Reproductive Health; 🇬🇧 Oxford, United Kingdom

Nottingham University Hospital NHS Trust; 🇬🇧 Nottingham, United Kingdom

Royal Preston Hospital; 🇬🇧 Preston, United Kingdom

Erasme Hospital; 🇧🇪 Brussels, Belgium

North Estonia Medical Centre Foundation Surgery Clinic; 🇪🇪 Tallinn, Estonia

Tartu University Hospital Womens Clinic; 🇪🇪 Tartu, Estonia