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

Primary Purpose

HPV Infection, CIN1

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ChAdOx1-HPV
MVA-HPV
Placebo
Sponsored by
Vaccitech (UK) Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV Infection

Eligibility Criteria

25 Years - 55 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • UZA
  • Erasme Hospital
  • UZ Brussel
  • UZ Gent
  • UZ Leuven
  • Parnu Hospital Womens and Childrens Clinic
  • East-Tallinn Central Hospital
  • North Estonia Medical Centre Foundation Surgery Clinic
  • Tartu University Hospital Womens Clinic
  • Aberdeen Royal Infirmary
  • University Hospital Bristol NHS Trust
  • Liverpool Women's NHS Foundation Trust
  • Royal Victoria Infirmary
  • Nottingham University Hospital NHS Trust
  • The University of Oxford, Nuffield Department of Women's & Reproductive Health
  • Royal Preston Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose

Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose

Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose

Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose

Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose

Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose

Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose

Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose

Group 6 Placebo Saline

Arm Description

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^7 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10) vp and MVA-HPV (1 x 10^8 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^7 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^8 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^8 pfu)

Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^8 pfu)

Sodium Chloride (0.9%)

Outcomes

Primary Outcome Measures

Incidence of adverse events to measure safety and reactogenicity
Measure of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse events reported.

Secondary Outcome Measures

Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development
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
The percentage of hrHPV infection clearance
Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)
The percentage of cervical lesions cleared as determined by colposcopy

Full Information

First Posted
October 22, 2020
Last Updated
March 28, 2023
Sponsor
Vaccitech (UK) Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04607850
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 16, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaccitech (UK) Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV Infection, CIN1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Lead in phase will be open label. Main phase and expansion phase will be blinded.
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lead-in Group A ChAdOx1-HPV low dose and MVA-HPV low dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^7 pfu)
Arm Title
Lead-in Group B ChAdOx1-HPV mid dose and MVA-HPV low dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
Arm Title
Lead-in Group C ChAdOx1-HPV high dose and MVA-HPV high dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10) vp and MVA-HPV (1 x 10^8 pfu)
Arm Title
Group 1 ChAdOx1-HPV mid dose and MVA-HPV low dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^7 pfu)
Arm Title
Group 2 ChAdOx1-HPV high dose and MVA-HPV low dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^7 pfu)
Arm Title
Group 3 ChAdOx1-HPV low dose and MVA-HPV high dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^8 vp) and MVA-HPV (1 x 10^8 pfu)
Arm Title
Group 4 ChAdOx1-HPV mid dose and MVA-HPV high dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^9 vp) and MVA-HPV (1 x 10^8 pfu)
Arm Title
Group 5 ChAdOx1-HPV high dose and MVA-HPV high dose
Arm Type
Experimental
Arm Description
Prime-boost vaccine doses: ChAdOx1-HPV (2 x 10^10 vp) and MVA-HPV (1 x 10^8 pfu)
Arm Title
Group 6 Placebo Saline
Arm Type
Placebo Comparator
Arm Description
Sodium Chloride (0.9%)
Intervention Type
Biological
Intervention Name(s)
ChAdOx1-HPV
Intervention Description
Trial vaccine
Intervention Type
Biological
Intervention Name(s)
MVA-HPV
Intervention Description
Trial vaccine
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Saline placebo vaccine
Primary Outcome Measure Information:
Title
Incidence of adverse events to measure safety and reactogenicity
Description
Measure of adverse events, serious adverse events (SAEs), ≥Grade 3 study vaccine-related adverse events reported.
Time Frame
3 months for the lead-in and 12 months for the main phase
Secondary Outcome Measure Information:
Title
Determine the dose of ChAdOx1-HPV plus MVA-HPV vaccines for further development
Description
Measurement of the highest multi-parameter index made of CD4+ magnitude, CD4+ avidity and CD8+ magnitude at peak timepoint
Time Frame
3 months for lead in phase and 12 months for main phase
Title
Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of high risk HPV infection
Description
The percentage of hrHPV infection clearance
Time Frame
12 months for main phase only
Title
Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on cervical intraepithelial neoplasia (CIN)
Description
The percentage of cervical lesions cleared as determined by colposcopy
Time Frame
12 months for main phase only
Other Pre-specified Outcome Measures:
Title
Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
Description
This will be assessed by measuring the individual phenotypic subsets of CD4+ and CD8+ T cells induced by vaccination
Time Frame
3 months for lead in phase and 12 months for main phase
Title
Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
Description
This will be assessed by measuring the innate immune response after vaccination compared to baseline
Time Frame
3 months for lead in phase and 12 months for main phase
Title
Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
Description
This will be assessed by measuring the T cell breadth of response to the components of the ChAdOx1-HPV plus MVA-HPV vaccines
Time Frame
3 months for lead in phase and 12 months for main phase
Title
Assess the complex cellular immune response generated by ChAdOx1-HPV plus MVA-HPV vaccines
Description
Immune responses after prime and boost vaccinations in cytobrush samples compared to baseline
Time Frame
3 months for lead in phase and 12 months for main phase

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Participants must have a cervix in order to participate.
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
UZA
City
Antwerp
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Erasme Hospital
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
UZ Brussel
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Parnu Hospital Womens and Childrens Clinic
City
Parnu
ZIP/Postal Code
80010
Country
Estonia
Facility Name
East-Tallinn Central Hospital
City
Tallinn
ZIP/Postal Code
10119
Country
Estonia
Facility Name
North Estonia Medical Centre Foundation Surgery Clinic
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Tartu University Hospital Womens Clinic
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
University Hospital Bristol NHS Trust
City
Bristol
ZIP/Postal Code
BS2 8EG
Country
United Kingdom
Facility Name
Liverpool Women's NHS Foundation Trust
City
Liverpool
ZIP/Postal Code
L8 7SS
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle Upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Nottingham University Hospital NHS Trust
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
The University of Oxford, Nuffield Department of Women's & Reproductive Health
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
ZIP/Postal Code
PR2 9HT
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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