A Non-Randomized, Open-Label Study to Assess the Reduction of Human Papillomavirus (HPV) Viral Infectivity and Transmission in HPV-Positive Women After Vaccination.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bellvitge University Hospital, Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

18 Aug 2022 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515228-36-00

EudraCT number

2021-005229-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

The main objective of the study is to demonstrate the reduction in infective capacity of body fluids (cervical, anal, urine, vulvar and oral samples) in adult women at least HPV 16 and/or, 18 positive after vaccination with 9vHPV in a three-dose regimen

Secondary objectives 2

1. -To determine HPV antibody levels before and after vaccination for each of the 9vHPV-covered HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58)
2. -Tertiary/Exploratory Objective. To demonstrate viral infectivity reduction in cervical, oral, urine, vulvar and anal samples from women positive for at least HPV 16 and/or 18 HPV before and after vaccination with 1-dose or 2-dose regimen of 9vHPV.

Conditions and MedDRA coding

Evaluation of the reduction of HPV infectivity and transmission before and after vaccination with 9vHPV

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Are women, aged 18 years or older for cohort 1 and cohort 2 , attending a routine cervical cancer screening visit or gynecological visit, are positive for HPV16 and/or HPV18 have been recently diagnosed for their HPV-positivity (within the last 10 months) and meet one of the following criteria: RIFT-HPV 1 cohort: non-vaccinated adult women aged 18 years or older, positive on cervix for HPV 16 and/or 18, with non apparent cervical lesion or with cervical lesion , eligible for conservative treatment. RIFT-HPV 2 cohort: non-vaccinated adult women aged 18 years or older, positive for HPV 16 and/or HPV 18 anal test with non-apparent anal lesions or with anal lesions eligible for conservative treatment. Or non-vaccinated adult women aged 18 years or older, positive for HPV 16 and/or HPV 18 cervical test with vulvar premalignant lesion or condylomas, associated to HPV infection.
2. Are judged to have no major health conditions (based on medical history, physical examination, and laboratory testing) that may compromise their capacity to comply with study procedures, as per Investigator’s judgement.
3. Provide written informed consent for their participation in the study.
4. Provide a frequent contact telephone number as well as an alternate means of contact (such as an alternate telephone number or email) for follow-up purposes.
5. Are planning to stay in their area of residence (near the study site) for the full duration of the study, so it is convenient for them to attend study visits at the site.

Exclusion criteria 10

1. Have any cervical lesion that requires clinical intervention within 7 months that could significantly affect cervical epithelia (and therefore, HPV viral production), such as cervical conization (RIFT-HPV Cohort 1).
2. Have a fever (defined as temperature ≥37.8°C) within the 24-hour period prior to the Day 1 visit (Visit 1)*.
3. Have a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention.
4. Are allergic to any vaccine component, including aluminium, yeast, or BENZONASETM (nuclease, Nicomedia [used to remove residual nucleic acids from this and other vaccines]). For this exclusion criterion, an allergy to vaccine components is defined as an allergic reaction that met the criteria for severe adverse event (SAE), defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or results in persistent or significant disability/incapacity.
5. Have known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection of study vaccine.
6. Have a history of splenectomy.
7. Have a history of ano-genital cancer or HPV-related head and neck cancer.
8. Are pregnant at the time of signing informed consent, are planning to become pregnant within the full duration of the study.
9. Have a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study or interfere with the subject’s compliance of study procedures for the full duration of the study, such that their inclusion in the study is not in the best interest of the subject and/or may compromise fulfilment of study’s objectives, by judgement of the Investigator.
10. Are, at the time of signing informed consent, using recreational or illicit drugs or have had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the Investigator that might interfere with her capacity to comply with study procedures. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems because of alcohol use.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. In-vitro infectivity evaluation (by expression of E1^E4 HPV biomarker in HaCaT keratinocytes) of cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination.
2. Detection of HPV 6/11/16/18/31/33/45/52/58 L1 antibodies in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination, using: -ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, -cLIA for all 9vHPV-covered types in samples from RIFT-HPV 1 study cohort. This endpoint will allow associating the reduction in viral infectivity with the presence of neutralizing antibodies.
3. -HPV16/18 virion detection (using ELISA, electronic microscopy) and HPV DNA detection and genotyping (using Anyplex/Allplex HPV28) in cervical, anal, vulvar, urine and oral samples collected before and after 9vHPV vaccination. This endpoint will allow to identify samples of subjects with a nonproductive viral infection or undergoing natural clearance, and distinguish them from samples of subjects with productive but reduced infection due to 9vHPV vaccination.

Secondary endpoints 1

1. -HPV 6/11/16/18/31/33/45/52/58 L1 antibody titration in serum samples collected before and after 9vHPV vaccination, using: -ELISA for types 16 and 18 in samples from RIFT-HPV 1 and 2 study cohorts, -cLIA for all 9vHPV-covered types in samples from RIFT-HPV 1 study cohort.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bellvitge University Hospital

Sponsor organisation

Bellvitge University Hospital

Address

Carrer De La Feixa Llarga S/N

City

L'Hospitalet De Llobregat

Postcode

08907

Country

Spain

Scientific contact point

Organisation

Bellvitge University Hospital

Contact name

Miguel Ángel Pavón Ribas

Public contact point

Organisation

Bellvitge University Hospital

Contact name

Miguel Ángel Pavón Ribas

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso Gallego

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso Gallego

Sponsor responsibilities

Article 77 compliance

Bellvitge University Hospital

Contact point sponsor

Bellvitge University Hospital

Article 77 implementation

Bellvitge University Hospital

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications