| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Persistent hrHPV infection in participants with low grade cervical lesions
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| E.1.1.1 | Medical condition in easily understood language |
| Persistent infection of the cervix with certain HPV strains. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10063001 |
| E.1.2 | Term | Human papilloma virus infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the safety and tolerability of ChAdOx1-HPV plus MVA-HPV vaccines when administered in a prime boost regimen. |
|
| E.2.2 | Secondary objectives of the trial |
• Determine the dose of ChAdOx1-HPV plus MVA HPV vaccines for further development
• Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on the clearance of hrHPV infection
• Determine the effect of ChAdOx1-HPV plus MVA-HPV vaccines on CIN (Cervical Intraepithelial Neoplasia) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants must meet all the following criteria to be eligible for the study:
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
5. Willing to abstain from sexual activity for 48 hours prior to all swabbing procedures.
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| E.4 | Principal exclusion criteria |
Participants who meet any of the following criteria are not eligible for the study:
1. Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness, including blood dyscracias.
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 HIV, hepatitis B, or HCV) indicating chronic infection.
4. Evidence of high grade cervical lesions by colposcopy or by 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.
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. Any history of receipt of any adenoviral or MVA based vaccine.
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) as evidenced by PCR laboratory testing.
13. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Safety and reactogenicity: incidence of adverse events, SAEs, ≥Grade 3 study vaccine-related adverse events within 4 weeks of vaccination and adverse events leading to study vaccine discontinuation |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Safety will be monitored throughout the study until 30 days after the last visit of each participant and reactogenicity measured on Day 0 and Day 28 for 30 minutes post vaccination, and also with patient diaries for 3 days starting on Days 1 and 29. |
|
| E.5.2 | Secondary end point(s) |
• Highest multi-parameter index made of CD4+ magnitude, CD4+ avidity and CD8+ magnitude at peak timepoint
• Percentage clearance of hrHPV infection at 12 months
• Percentage of cervival lesions cleared as determined by colposcopy
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Multi-parameter index tested on samples collected on Days 0, 28 and 35 and Month 3 as well as Month 12 in the Main phase.
Vaginal/endocervical HPV swabs taken collected at screening, M3, M6, M9 and M12.
Percentage lesion clearance determined at Month 6 and 12. HPV clearance is determined at all swabbing visits. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Dose-ranging, the Lead-in Phase is an open label design |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 7 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| The end of trial is achieved when the database is locked. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 5 |
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