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

• ClinicalTrials.gov Identifier: NCT04607850
• Recruitment Status: Completed
• First Posted: October 29, 2020
• Last Update Posted: January 19, 2024
• Sponsor: Barinthus Biotherapeutics
• Information provided by (Responsible Party): Barinthus Biotherapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HPV Infection; CIN1	Biological: ChAdOx1-HPV; Biological: MVA-HPV; Biological: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Lead in phase will be open label. Main phase and expansion phase will be blinded.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 16, 2021
• Actual Primary Completion Date: January 16, 2024
• Actual Study Completion Date: January 16, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^7 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10) vp and MVA-HPV (1 x 10^8 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^7 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^8 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^8 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Experimental: Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose; Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^8 pfu)	Biological: ChAdOx1-HPV; Trial vaccine; Biological: MVA-HPV; Trial vaccine
Placebo Comparator: Group 6 Placebo Saline; Sodium Chloride (0.9%)	Biological: Placebo; Saline placebo vaccine

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events to measure safety and reactogenicity [ Time Frame: 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 :

1. Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development [ Time Frame: 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
2. Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection [ Time Frame: 12 months for main phase only ]
   The percentage of hrHPV infection clearance
3. Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN) [ Time Frame: 12 months for main phase only ]
   The percentage of cervical lesions cleared as determined by colposcopy

Other Outcome Measures:

1. Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines [ Time Frame: 3 months for lead in phase and 12 months for main phase ]
   This will be assessed by measuring the individual phenotypic subsets of CD4+ and CD8+ T cells induced by vaccination
2. Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines [ Time Frame: 3 months for lead in phase and 12 months for main phase ]
   This will be assessed by measuring the innate immune response after vaccination compared to baseline
3. Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines [ Time Frame: 3 months for lead in phase and 12 months for main phase ]
   This will be assessed by measuring the T cell breadth of response to the components of the ChAdOx1-HPV plus MVA-HPV vaccines
4. Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines [ Time Frame: 3 months for lead in phase and 12 months for main phase ]
   Immune responses after prime and boost vaccinations in cytobrush samples compared to baseline

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Participants must have a cervix in order to participate.
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Belgium

UZA

Antwerp, Belgium, 2650

Erasme Hospital

Brussels, Belgium, 1070

UZ Brussel

Brussels, Belgium, 1090

UZ Gent

Gent, Belgium, 9000

UZ Leuven

Leuven, Belgium, 3000

Estonia

Parnu Hospital Womens and Childrens Clinic

Parnu, Estonia, 80010

East-Tallinn Central Hospital

Tallinn, Estonia, 10119

North Estonia Medical Centre Foundation Surgery Clinic

Tallinn, Estonia, 13419

Tartu University Hospital Womens Clinic

Tartu, Estonia, 51014

United Kingdom

Aberdeen Royal Infirmary

Aberdeen, United Kingdom, AB25 2ZN

University Hospital Bristol NHS Trust

Bristol, United Kingdom, BS2 8EG

Liverpool Women's NHS Foundation Trust

Liverpool, United Kingdom, L8 7SS

Royal Victoria Infirmary

Newcastle Upon Tyne, United Kingdom, NE1 4LP

Nottingham University Hospital NHS Trust

Nottingham, United Kingdom, NG5 1PB

The University of Oxford, Nuffield Department of Women's & Reproductive Health

Oxford, United Kingdom, OX3 9DU

Royal Preston Hospital

Preston, United Kingdom, PR2 9HT

Sponsors and Collaborators

Barinthus Biotherapeutics

More Information

• Responsible Party: Barinthus Biotherapeutics
• ClinicalTrials.gov Identifier: NCT04607850
• Other Study ID Numbers: HPV001
• First Posted: October 29, 2020
• Last Update Posted: January 19, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Papillomavirus Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes